document_title: Bone

question_text: what do you call the young bone-forming cells

question_tokens: what do you call the young bone-forming cells

text: Bone

text: Structure[edit]

text: Bone is not uniformly solid, but consists of a flexible matrix (about 30%) and bound minerals (about 70%) which are intricately woven and endlessly remodeled by a group of specialized bone cells. Their unique composition and design allows bones to be relatively hard and strong, while remaining lightweight.

text: Bone matrix is 90 to 95% composed of elastic collagen fibers, also known as ossein,[3] and the remainder is ground substance.[4]  The elasticity of collagen improves fracture resistance.[5] The matrix is hardened by the binding of inorganic mineral salt calcium phosphate in a chemical arrangement known as calcium hydroxylapatite. It is the bone mineralization that give bones rigidity.

text: Bone is actively constructed and remodeled throughout life by special bone cells known as osteoblasts and osteoclasts. Within any single bone, the tissue is woven into two main patterns, known cortical and cancellous bone, and each with different appearance and characteristics.

text: Cortical bone[edit]

text: The hard outer layer of bones is composed of cortical bone also called compact bone being much denser than cancellous bone. It forms the hard exterior (cortex) of bones. The cortical bone gives bone its smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adult human skeleton.[citation needed] It facilitates bone's main functions: to support the whole body, protect organs, provide levers for movement, and store and release chemical elements, mainly calcium. It consists of multiple microscopic columns, each called an osteon. Each column is multiple layers of osteoblasts and osteocytes around a central canal called the haversian canal. Volkmann's canals at right angles connect the osteons together. The columns are metabolically active, and as bone is reabsorbed and created the nature and location of the cells within the osteon will change. Cortical bone is covered by a periosteum on its outer surface, and an endosteum on its inner surface. The endosteum is the boundary between the cortical bone and the cancellous bone.[6] The primary anatomical and functional unit of cortical bone is the osteon.

text: Cancellous bone[edit]

text: Cancellous bone, also called trabecular or spongy bone, [6] is the internal tissue of the skeletal bone and is an open cell porous network. Cancellous bone has a higher surface-area-to-volume ratio than cortical bone because it is less dense. This makes it weaker and more flexible. The greater surface area also makes it suitable for metabolic activities such as the exchange of calcium ions. Cancellous bone is typically found at the ends of long bones, near joints and in the interior of vertebrae. Cancellous bone is highly vascular and often contains red bone marrow where haematopoiesis, the production of blood cells, occurs. The primary anatomical and functional unit of cancellous bone is the trabecula. The trabeculae are aligned towards the mechanical load distribution that a bone experiences within long bones such as the femur.  As far as short bones are concerned, trabecular alignment has been studied in the vertebral pedicle.[7] Thin formations of osteoblasts covered in endosteum create an irregular network of spaces,[8] known as trabeculae. Within these spaces are bone marrow and hematopoietic stem cells that give rise to platelets, red blood cells and white blood cells.[8] Trabecular marrow is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass but has nearly ten times the surface area of compact bone.[9]

text: The words cancellous and trabecular refer to the tiny lattice-shaped units (trabeculae)  that form the tissue. It was first illustrated accurately in the engravings of Crisóstomo Martinez.[10]

text: Bone marrow[edit]

text: Bone marrow, also known as myeloid tissue in red bone marrow,  can be found in almost any bone that holds cancellous tissue.  In newborns, all such bones are filled exclusively with red marrow or hematopoietic marrow, but as the child ages the hematopoietic fraction decreases in quantity and the fatty/ yellow fraction called marrow adipose tissue (MAT) increases in quantity.  In adults, red marrow is mostly found in the bone marrow of the femur, the ribs, the vertebrae and pelvic bones.[11]

text: Bone cells[edit]

text: Bone is a metabolically active tissue composed of several types of cells. These cells include osteoblasts, which are involved in the creation and mineralization of bone tissue, osteocytes, and osteoclasts, which are involved in the reabsorption of bone tissue. Osteoblasts and osteocytes are derived from osteoprogenitor cells, but osteoclasts are derived from the same cells that differentiate to form macrophages and monocytes.[12] Within the marrow of the bone there are also hematopoietic stem cells. These cells give rise to other cells, including white blood cells, red blood cells, and platelets.[13]

text: Osteoblast[edit]

text: Osteoblasts are mononucleate bone-forming cells. They are located on the surface of osteon seams and make a protein mixture known as osteoid, which mineralizes to become bone.[14] The osteoid seam is a narrow region of newly formed organic matrix, not yet mineralized, located on the surface of a bone. Osteoid is primarily composed of Type I collagen. Osteoblasts also manufacture hormones, such as prostaglandins, to act on the bone itself. The osteoblast creates and repairs new bone by actually building around itself. First, the osteoblast puts up collagen fibers. These collagen fibers are used as a framework for the osteoblasts' work. The osteoblast then deposits calcium phosphate which is hardened by hydroxide and bicarbonate ions. The brand new bone created by the osteoblast is called osteoid.[15] Once the osteoblast is finished working it is actually trapped inside the bone once it hardens. When the osteoblast becomes trapped, it becomes known as an osteocyte.[16] Other osteoblasts remain on the top of the new bone and are used to protect the underlying bone, these become known as lining cells.

text: Osteocyte[edit]

text: Osteocytes are mostly inactive osteoblasts.[12] Osteocytes originate from osteoblasts that have migrated into and become trapped and surrounded by bone matrix that they themselves produced.[6] The spaces they occupy are known as lacunae. Osteocytes have many processes that reach out to meet osteoblasts and other osteocytes probably for the purposes of communication.[citation needed] Osteocytes remain in contact with other cells in the bone through gap junctions—coupled cell processes—which pass through small channels in the bone matrix called the canaliculi.

text: Osteoclast[edit]

text: Osteoclasts are very large multinucleate cells that are responsible for the breakdown of bones by the process of bone resorption. New bone is then formed by the osteoblasts. Bone is constantly remodelled by the resorption of osteoclasts and created by osteoblasts.[12] Osteoclasts are large cells with multiple nuclei located on bone surfaces in what are called Howship's lacunae (or resorption pits). These lacunae are the result of surrounding bone tissue that has been reabsorbed.[17] Because the osteoclasts are derived from a monocyte stem-cell lineage, they are equipped with phagocytic-like mechanisms similar to circulating macrophages.[12] Osteoclasts mature and/or migrate to discrete bone surfaces. Upon arrival, active enzymes, such as tartrate resistant acid phosphatase, are secreted against the mineral substrate.[citation needed] The reabsorption of bone by osteoclasts also plays a role in calcium homeostasis.[17]

text: Extracellular matrix[edit]

text: Bones consist of living cells embedded in a mineralized organic matrix. This matrix consists of organic components, mainly Type I collagen – "organic" referring to materials produced as a result of the human body – and inorganic components, primarily hydroxyapatite and other salts of calcium and phosphate. Above 30% of the acellular part of bone consists of the organic components, and 70% of salts.[18] The collagen fibers give bone its tensile strength, and the interspersed crystals of hydroxyapatite give bone its compressive strength. These effects are synergistic.[18]

text: The inorganic composition of bone (bone mineral) is primarily formed from salts of calcium and phosphate, the major salt being hydroxyapatite (Ca10(PO4)6(OH)2).[18] The exact composition of the matrix may be subject to change over time due to nutrition and biomineralization, with the ratio of calcium to phosphate varying between 1.3 and 2.0 (per weight), and trace minerals such as magnesium, sodium, potassium and carbonate also being found.[18]

text: Type I collagen composes 90–95% of the organic matrix, with remainder of the matrix being a homogenous liquid called ground substance consisting of proteoglycans such as hyaluronic acid and chondroitin sulfate ,[18] as well as non-collagenous proteins such as osteocalcin, osteopontin or bone sialoprotein . Collagen consists of strands of repeating units, which give bone tensile strength, and are arranged in an overlapping fashion that prevents shear stress. The function of ground substance is not fully known.[18] Two types of bone can be identified microscopically according to the arrangement of collagen: woven and lamellar.

text:
Woven bone, (also known as fibrous bone) which is characterized by a haphazard organization of collagen fibers and is mechanically weak[19]
Lamellar bone, which has a regular parallel alignment of collagen into sheets ("lamellae") and is mechanically strong[19]

tag: ul

text: Woven bone is produced when osteoblasts produce osteoid rapidly, which occurs initially in all fetal bones, but is later replaced by more resilient lamellar bone. In adults woven bone is created after fractures or in Paget's disease. Woven bone is weaker, with a smaller number of randomly oriented collagen fibers, but forms quickly; it is for this appearance of the fibrous matrix that the bone is termed woven. It is soon replaced by lamellar bone, which is highly organized in concentric sheets with a much lower proportion of osteocytes to surrounding tissue. Lamellar bone, which makes its first appearance in humans in the fetus during the third trimester,[20] is stronger and filled with many collagen fibers parallel to other fibers in the same layer (these parallel columns are called osteons).  In cross-section, the fibers run in opposite directions in alternating layers, much like in plywood, assisting in the bone's ability to resist torsion forces. After a fracture, woven bone forms initially and is gradually replaced by lamellar bone during a process known as "bony substitution." Compared to woven bone, lamellar bone formation takes place more slowly. The orderly deposition of collagen fibers restricts the formation of osteoid to about 1 to 2 µm per day. Lamellar bone also requires a relatively flat surface to lay the collagen fibers in parallel or concentric layers.[citation needed]

text: Deposition[edit]

text: The extracellular matrix of bone is laid down by osteoblasts, which secrete both collagen and ground substance. These synthesise collagen within the cell, and then secrete collagen fibrils. The collagen fibres rapidly polymerise to form collagen strands. At this stage they are not yet mineralised, and are called "osteoid". Around the strands calcium and phosphate precipitate on the surface of these strands, within days to weeks becoming crystals of hydroxyapatite.[18]

text: In order to mineralise the bone, the osteoblasts secrete vesicles containing alkaline phosphatase. This cleaves the phosphate groups and acts as the foci for calcium and phosphate deposition. The vesicles then rupture and act as a centre for crystals to grow on. More particularly, bone mineral is formed from globular and plate structures.[21][22]

text: Types[edit]

text: There are five types of bones in the human body: long, short, flat, irregular, and sesamoid.[23]

text:
Long bones are characterized by a shaft, the diaphysis, that is much longer than its width; and by an epiphysis, a rounded head at each end of the shaft. They are made up mostly of compact bone, with lesser amounts of marrow, located within the medullary cavity, and areas of spongy, cancellous bone at the ends of the bones.[24]     Most bones of the limbs, including those of the fingers and toes, are long bones. The exceptions are the eight carpal bones of the wrist, the seven articulating tarsal bones of the ankle and the sesamoid bone of the kneecap. Long bones such as the clavicle, that have a differently shaped shaft or ends are also called modified long bones.
Short bones are roughly cube-shaped, and have only a thin layer of compact bone surrounding a spongy interior.  The bones of the wrist and ankle are short bones.
Flat bones are thin and generally curved, with two parallel layers of compact bones sandwiching a layer of spongy bone.  Most of the bones of the skull are flat bones, as is the sternum.[25]
Sesamoid bones are bones embedded in tendons.  Since they act to hold the tendon further away from the joint, the angle of the tendon is increased and thus the leverage of the muscle is increased.  Examples of sesamoid bones are the patella and the pisiform.[26]
Irregular bones do not fit into the above categories.  They consist of thin layers of compact bone surrounding a spongy interior.  As implied by the name, their shapes are irregular and complicated. Often this irregular shape is due to their many centers of ossification or because they contain bony sinuses.  The bones of the spine, pelvis, and some bones of the skull are irregular bones. Examples include the ethmoid and sphenoid bones.[27]

text: Terminology[edit]

text: In the study of anatomy, anatomists use a number of anatomical terms to describe the appearance, shape and function of bones. Other anatomical terms are also used to describe the location of bones. Like other anatomical terms, many of these derive from Latin and Greek. Some anatomists still use Latin to refer to bones. The term "osseous", and the prefix "osteo-", referring to things related to bone, are still used commonly today.

text: Some examples of terms used to describe bones include the term "foramen" to describe a hole through which something passes, and a "canal" or "meatus" to describe a tunnel-like structure. A protrusion from a bone can be called a number of terms, including a "condyle", "crest", "spine", "eminence", "tubercle" or "tuberosity", depending on the protrusion's shape and location. In general, long bones are said to have a "head", "neck", and "body".

text: When two bones join together, they are said to "articulate". If the two bones have a fibrous connection and are relatively immobile, then the joint is called a "suture".

text: Development[edit]

text: The formation of bone is called ossification. During the fetal stage of development this occurs by two processes: intramembranous ossification and endochondral ossification.[citation needed] Intramembranous ossification involves the formation of bone from connective tissue whereas endochondral ossification involves the formation of bone from cartilage.

text: Intramembranous ossification mainly occurs during formation of the flat bones of the skull but also the mandible, maxilla, and clavicles; the bone is formed from connective tissue such as mesenchyme tissue rather than from cartilage. The process includes: the development of the ossification center, calcification, trabeculae formation and the development of the periosteum.[citation needed]

text: Endochondral ossification occurs in long bones and most other bones in the body; it involves the development of bone from cartilage. This process includes the development of a cartilage model, its growth and development, development of the primary and secondary ossification centers, and the formation of articular cartilage and the epiphyseal plates.[citation needed]

text: Endochondral ossification begins with points in the cartilage called "primary ossification centers." They mostly appear during fetal development, though a few short bones begin their primary ossification after birth.  They are responsible for the formation of the diaphyses of long bones, short bones and certain parts of irregular bones.  Secondary ossification occurs after birth, and forms the epiphyses of long bones and the extremities of irregular and flat bones.  The diaphysis and both epiphyses of a long bone are separated by a growing zone of cartilage (the epiphyseal plate). At skeletal maturity (18 to 25 years of age), all of the cartilage is replaced by bone, fusing the diaphysis and both epiphyses together (epiphyseal closure).[citation needed] In the upper limbs, only the diaphyses of the long bones and scapula are ossified.  The epiphyses, carpal bones, coracoid process, medial border of the scapula, and acromion are still cartilaginous.[28]

text: The following steps are followed in the conversion of cartilage to bone:

text:
Zone of reserve cartilage. This region, farthest from the marrow cavity, consists of typical hyaline cartilage that as yet shows no sign of transforming into bone.[29]
Zone of cell proliferation. A little closer to the marrow cavity, chondrocytes multiply and arrange themselves into longitudinal columns of flattened lacunae.[29]
Zone of cell hypertrophy.  Next, the chondrocytes cease to divide and begin to hypertrophy (enlarge), much like they do in the primary ossification center of the fetus.  The walls of the matrix between lacunae become very thin.[29]
Zone of calcification.  Minerals are deposited in the matrix between the columns of lacunae and calcify the cartilage.  These are not the permanent mineral deposits of bone, but only a temporary support for the cartilage that would otherwise soon be weakened by the breakdown of the enlarged lacunae.[29]
Zone of bone deposition.  Within each column, the walls between the lacunae break down and the chondrocytes die.  This converts each column into a longitudinal channel, which is immediately invaded by blood vessels and marrow from the marrow cavity.  Osteoblasts line up along the walls of these channels and begin depositing concentric lamellae of matrix, while osteoclasts dissolve the temporarily calcified cartilage.[29]

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text: Function[edit]

text:
Functions of Bone

Mechanical
Protection
Gives structure
Facilitates movement
Facilitates hearing

Synthetic
Contains bone marrow

Metabolic
Stores calcium
Helps regulate the acid-base balance

text: Bones have a variety of functions:

text: Mechanical[edit]

text: Bones serve a variety of mechanical functions. Together the bones in the body form the skeleton. They provide a frame to keep the body supported, and an attachment point for skeletal muscles, tendons, ligaments and joints, which function together to generate and transfer forces so that individual body parts or the whole body can be manipulated in three-dimensional space (the interaction between bone and muscle is studied in biomechanics).

text: Bones protect internal organs, such as the skull protecting the brain or the ribs protecting the heart and lungs. Because of the way that bone is formed, bone has a high compressive strength of about 170 MPa (1800 kgf/cm²),[5] poor tensile strength of 104–121 MPa, and a very low shear stress strength (51.6 MPa).[30][31] This means that bone resists pushing(compressional) stress well, resist pulling(tensional) stress less well, but only poorly resists shear stress (such as due to torsional loads). While bone is essentially brittle, bone does have a significant degree of elasticity, contributed chiefly by collagen. The macroscopic yield strength of cancellous bone has been investigated using high resolution computer models.[32]

text: Mechanically, bones also have a special role in hearing. The ossicles are three small bones in the middle ear which are involved in sound transduction.

text: Synthetic[edit]

text: The cancellous part of bones contain bone marrow. Bone marrow produces blood cells in a process called hematopoiesis.[33] Blood cells that are created in bone marrow include red blood cells, platelets and white blood cells.[34] Progenitor cells such as the hematopoietic stem cell divide in a process called mitosis to produce precursor cells. These include precursors which eventually give rise to white blood cells, and erythroblasts which give rise to red blood cells.[35] Unlike red and white blood cells, created by mitosis, platelets are shed from very large cells called megakaryocytes.[36] This process of progressive differentiation occurs within the bone marrow. After the cells are matured, they enter the circulation.[37] Every day, over 2.5 billion red blood cells and platelets, and 50–100 billion granulocytes are produced in this way.[13]

text: As well as creating cells, bone marrow is also one of the major sites where defective or aged red blood cells are destroyed.[13]

text: Metabolic[edit]

text: Mineral storage — bones act as reserves of minerals important for the body, most notably calcium and phosphorus.[38][citation needed][39]

text:
°Determined by the species, age, and the type of bone, bone cells make up to 15 percent of the bone.
Growth factor storage — mineralized bone matrix stores important growth factors such as insulin-like growth factors, transforming growth factor, bone morphogenetic proteins and others.[citation needed]

text:
Fat storage —marrow adipose tissue (MAT) acts as a storage reserve of fatty acids.[40]
Acid-base balance — bone buffers the blood against excessive pH changes by absorbing or releasing alkaline salts.[citation needed]
Detoxification — bone tissues can also store heavy metals and other foreign elements, removing them from the blood and reducing their effects on other tissues. These can later be gradually released for excretion.[citation needed]
Endocrine organ — bone controls phosphate metabolism by releasing fibroblast growth factor – 23 (FGF-23), which acts on kidneys to reduce phosphate reabsorption. Bone cells also release a hormone called osteocalcin, which contributes to the regulation of blood sugar (glucose) and fat deposition. Osteocalcin increases both the insulin secretion and sensitivity, in addition to boosting the number of insulin-producing cells and reducing stores of fat.[41]
Calcium balance—The process of bone resorption by the osteoclasts releases stored calcium into the systemic circulation and is an important process in regulating calcium balance. As bone formation actively fixes circulating calcium in its mineral form, removing it from the bloodstream, resorption actively unfixes it thereby increasing circulating calcium levels. These processes occur in tandem at site-specific locations.[citation needed]

text: Remodeling[edit]

text: Bone is constantly being created and replaced in a process known as remodeling. This ongoing turnover of bone is a process of resorption followed by replacement of bone with little change in shape. This is accomplished through osteoblasts and osteoclasts. Cells are stimulated by a variety of signals, and together referred to as a remodeling unit. Approximately 10% of the skeletal mass of an adult is remodelled each year.[42] The purpose of remodeling is to regulate calcium homeostasis, repair microdamaged bones from everyday stress, and to shape the skeleton during growth.[citation needed] Repeated stress, such as weight-bearing exercise or bone healing, results in the bone thickening at the points of maximum stress (Wolff's law). It has been hypothesized that this is a result of bone's piezoelectric properties, which cause bone to generate small electrical potentials under stress.[43]

text: The action of osteoblasts and osteoclasts are controlled by a number of chemical enzymes that either promote or inhibit the activity of the bone remodeling cells, controlling the rate at which bone is made, destroyed, or changed in shape. The cells also use paracrine signalling to control the activity of each other.[citation needed] For example, the rate at which osteoclasts resorb bone is inhibited by calcitonin and osteoprotegerin.  Calcitonin is produced by parafollicular cells in the thyroid gland, and can bind to receptors on osteoclasts to directly inhibit osteoclast activity. Osteoprotegerin is secreted by osteoblasts and is able to bind RANK-L, inhibiting osteoclast stimulation.[44]

text: Osteoblasts can also be stimulated to increase bone mass through increased secretion of osteoid and by inhibiting the ability of osteoclasts to break down osseous tissue.[citation needed] Increased secretion of osteoid is stimulated by the secretion of growth hormone by the pituitary, thyroid hormone and the sex hormones (estrogens and androgens). These hormones also promote increased secretion of osteoprotegerin.[44] Osteoblasts can also be induced to secrete a number of cytokines that promote reabsorbtion of bone by stimulating osteoclast activity and differentiation from progenitor cells. Vitamin D, parathyroid hormone and stimulation from osteocytes induce osteoblasts to increase secretion of RANK-ligand and interleukin 6, which cytokines then stimulate increased reabsorption of bone by osteoclasts. These same compounds also increase secretion of macrophage colony-stimulating factor by osteoblasts, which promotes the differentiation of progenitor cells into osteoclasts, and decrease secretion of osteoprotegerin.[citation needed]

text: Bone volume[edit]

text: Bone volume is determined by the rates of bone formation and bone resorption. Recent research has suggested that certain growth factors may work to locally alter bone formation by increasing osteoblast activity. Numerous bone-derived growth factors have been isolated and classified via bone cultures. These factors include insulin-like growth factors I and II, transforming growth factor-beta, fibroblast growth factor, platelet-derived growth factor, and bone morphogenetic proteins.[45] Evidence suggests that bone cells produce growth factors for extracellular storage in the bone matrix. The release of these growth factors from the bone matrix could cause the proliferation of osteoblast precursors. Essentially, bone growth factors may act as potential determinants of local bone formation.[45] Research has suggested that cancellous bone volume in postemenopausal osteoporosis may be determined by the relationship between the total bone forming surface and the percent of surface resorption.[46]

text: Clinical significance[edit]

text: A number of diseases can affect bone, including arthritis, fractures, infections, osteoporosis and tumours. Conditions relating to bone can be managed by a variety of doctors, including rheumatologists for joints, and orthopedic surgeons, who may conduct surgery to fix broken bones. Other doctors, such as rehabilitation specialists may be involved in recovery, radiologists in interpreting the findings on imaging, and pathologists in investigating the cause of the disease, and family doctors may play a role in preventing complications of bone disease such as osteoporosis.

text: When a doctor sees a patient, a history and exam will be taken. Bones are then often imaged, called radiography. This might include ultrasound X-ray, CT scan, MRI scan and other imaging such as a Bone scan, which may be used to investigate cancer.[47] Other tests such as a blood test for autoimmune markers may be taken, or a synovial fluid aspirate may be taken.[47]

text: Fractures[edit]

text:
In normal bone, fractures occur when there is significant force applied, or repetitive trauma over a long time. Fractures can also occur when a bone is weakened, such as with osteoporosis, or when there is a structural problem, such as when the bone remodels excessively (such as Paget's disease) or is the site of the growth of cancer.[48] Common fractures include wrist fractures and hip fractures, associated with osteoporosis, vertebral fractures associated with high-energy trauma and cancer, and fractures of long-bones. Not all fractures are painful.[48] When serious, depending on the fractures type and location, complications may include flail chest, compartment syndromes or fat embolism.
Compound fractures involve the bone's penetration through the skin. Some complex fractures can be treated by the use of bone grafting procedures that replace missing bone portions.

text: Fractures and their underlying causes can be investigated by X-rays, CT scans and MRIs.[48] Fractures are described by their location and shape, and several classification systems exist, depending on the location of the fracture. A common long bone fracture in children is a Salter–Harris fracture.[49] When fractures are managed, pain relief is often given, and the fractured area is often immobilised. This is to promote bone healing. In addition, surgical measures such as internal fixation may be used. Because of the immobilisation, people with fractures are often advised to undergo rehabilitation.[48]

text: Tumors[edit]

text: There are several types of tumour that can affect bone; examples of benign bone tumours include osteoma, osteoid osteoma, osteochondroma, osteoblastoma, enchondroma, giant cell tumor of bone, and aneurysmal bone cyst.[50]

text: Cancer[edit]

text: Cancer can arise in bone tissue, and bones are also a common site for other cancers to spread (metastasise) to.[51] Cancers that arise in bone are called "primary" cancers, although such cancers are rare.[51] Metastases within bone are "secondary" cancers, with the most common being breast cancer, lung cancer, prostate cancer, thyroid cancer, and kidney cancer.[51] Secondary cancers that affect bone can either destroy bone (called a "lytic" cancer) or create bone (a "sclerotic" cancer). Cancers of the bone marrow inside the bone can also affect bone tissue, examples including leukemia and multiple myeloma. Bone may also be affected by cancers in other parts of the body. Cancers in other parts of the body may release parathyroid hormone or parathyroid hormone-related peptide. This increases bone reabsorption, and can lead to bone fractures.

text: Bone tissue that is destroyed or altered as a result of cancers is distorted, weakened, and more prone to fracture. This may lead to compression of the spinal cord, destruction of the marrow resulting in bruising, bleeding and immunosuppression, and is one cause of bone pain. If the cancer is metastatic, then there might be other symptoms depending on the site of the original cancer. Some bone cancers can also be felt.

text: Cancers of the bone are managed according to their type, their stage, prognosis, and what symptoms they cause. Many primary cancers of bone are treated with radiotherapy. Cancers of bone marrow may be treated with chemotherapy, and other forms of targeted therapy such as immunotherapy may be used.[52] Palliative care, which focuses on maximising a person's quality of life, may play a role in management, particularly if the likelihood of survival within five years is poor.

text: Painful conditions[edit]

text:
Osteomyelitis is inflammation of the bone or bone marrow due to bacterial infection.
Osteogenesis imperfecta
Osteochondritis dissecans
Arthritis
Ankylosing spondylitis
Skeletal fluorosis is a bone disease caused by an excessive accumulation of fluoride in the bones. In advanced cases, skeletal fluorosis damages bones and joints and is painful.

text: Osteoporosis[edit]

text: Osteoporosis is a disease of bone where there is reduced bone mineral density, increasing the likelihood of fractures.[53]  Osteoporosis is defined in women by the World Health Organization as a bone mineral density of 2.5 standard deviations below peak bone mass, relative to the age and sex-matched average. This density is measured using dual energy X-ray absorptiometry (DEXA), with the term "established osteoporosis" including the presence of a fragility fracture.[54] Osteoporosis is most common in women after menopause, when it is called "postmenopausal osteoporosis", but may develop in men and premenopausal women in the presence of particular hormonal disorders and other chronic diseases or as a result of smoking and medications, specifically glucocorticoids.[53] Osteoporosis usually has no symptoms until a fracture occurs.[53] For this reason, DEXA scans are often done in people with one or more risk factors, who have developed osteoporosis and are at risk of fracture.[53]

text: Osteoporosis treatment includes advice to stop smoking, decrease alcohol consumption, exercise regularly, and have a healthy diet. Calcium and trace mineral supplements may also be advised, as may Vitamin D. When medication is used, it may include bisphosphonates, Strontium ranelate, and hormone replacement therapy.[55]

text: Osteopathy[edit]

text: Osteopathic medicine is a school of medical thought originally developed based on the idea of the link between the musculoskeletal system and overall health, but now very similar to mainstream medicine. As of  2012[update], over 77,000 physicians in the United States are trained in Osteopathic medicine colleges.[56]

text: Osteology[edit]

text: The study of bones and teeth is referred to as osteology. It is frequently used in anthropology, archeology and forensic science for a variety of tasks. This can include determining the nutritional, health, age or injury status of the individual the bones were taken from. Preparing fleshed bones for these types of studies can involve the process of maceration.

text: Typically anthropologists and archeologists study bone tools made by Homo sapiens and Homo neanderthalensis.  Bones can serve a number of uses such as projectile points or artistic pigments, and can also be made from external bones such as antlers.

text: Other animals[edit]

text: Bird skeletons are very lightweight. Their bones are smaller and thinner, to aid flight. Among mammals, bats come closest to birds in terms of bone density, suggesting that small dense bones are a flight adaptation. Many bird bones have little marrow due to their being hollow.[57]

text: A bird's beak is primarily made of bone as projections of the mandibles which are covered in keratin.

text: A deer's antlers are composed of bone which is an unusual example of bone being outside the skin of the animal once the velvet is shed.[58]

text: The extinct predatory fish Dunkleosteus had sharp edges of hard exposed bone along its jaws.[59][60]

text: Many animals possess an exoskeleton that is not made of bone. These include insects and crustaceans.

text: The proportion of cortical bone that is 80% in the human skeleton may be much lower in other animals, especially in marine mammals and marine turtles, or in various Mesozoic marine reptiles, such as ichthyosaurs,[61] among others.[62]

text: Many animals particularly herbivores practice osteophagy – the eating of bones. This is presumably carried out in order to replenish lacking phosphate.

text: Many bone diseases that affect humans also affect other vertebrates – an example of one disorder is skeletal flurosis.

text: Society and culture[edit]

text: Bones from slaughtered animals have a number of uses. In prehistoric times, they have been used for making bone tools.[citation needed] They have further been used in bone carving, already important in prehistoric art, and also in modern time as crafting materials for buttons, beads, handles, bobbins, calculation aids, head nuts, dice, poker chips, pick-up sticks, ornaments, etc. A special genre is scrimshaw.[citation needed]

text: Bone glue can be made by prolonged boiling of ground or cracked bones, followed by filtering and evaporation to thicken the resulting fluid. Historically once important, bone glue and other animal glues today have only a few specialized uses, such as in antiques restoration. Essentially the same process, with further refinement, thickening and drying, is used to make gelatin.

text: Broth is made by simmering several ingredients for a long time, traditionally including bones.

text: Ground bones are used as an organic phosphorus-nitrogen fertilizer and as additive in animal feed. Bones, in particular after calcination to bone ash, are used as source of calcium phosphate for the production of bone china and previously also phosphorus chemicals.[citation needed]

text: Bone char, a porous, black, granular material primarily used for filtration and also as a black pigment, is produced by charring mammal bones.

text: Oracle bone script was a writing system used in Ancient china based on inscriptions in bones.

text: To point the bone at someone is considered bad luck in some cultures, such as Australian aborigines, such as by the Kurdaitcha.

text: The wishbones of fowl have been used for divination, and are still customarily used in a tradition to determine which one of two people pulling on either prong of the bone may make a wish.

text:
Various cultures throughout history have adopted the custom of shaping an infant's head by the practice of artificial cranial deformation.  A widely practised
custom in China was that of foot binding to limit the normal growth of the foot.

text: Additional images[edit]

text:
Cells in bone marrow

Scanning electron microscope of bone at 100x magnification


document_title: P.S. I Love You (1934 song)

question_text: who sang the song ps i love you

question_tokens: who sang the song ps i love you

root

text: P.S. I Love You (1934 song)

text: "P.S. I Love You" is a popular song. The music was written by Gordon Jenkins, the lyrics by Johnny Mercer. The song was published in 1934.[1][2]

tag: p

text: The original hit version in the 1930s was recorded by Rudy Vallée. It was revived in the 1950s by The Hilltoppers and in the 1960s by The Vogues, and again in 1984 by country music singer Tom T. Hall. A number of other versions have also been recorded.

text: Recorded versions[edit]

text:
The Angels released a version in 1960 while they were still called The Starlets. The version went to #106 in the U.S.
Rosemary Clooney - Rosemary Clooney Sings the Lyrics of Johnny Mercer (1988)
Bing Crosby
Bob Dylan - Triplicate (2017)
The Four Vagabonds - Apollo 1057 (1947); reissued Lloyds 45-102 (1953)
Tom T. Hall
Lionel Hampton
The Hilltoppers
Don Burke and the Four Hits and a Miss with Gordon Jenkins and his orchestra
Billie Holiday recorded the song for Verve Records on September 3, 1954 in Los Angeles with Her Orchestra, consisting of Harry Edison on trumpet, Willie Smith on alto saxophone, Bobby Tucker on piano, Barney Kessel on guitar, Red Callender on bass and Chico Hamilton on drums. The song is featured on the 1999 reissue of Lady Sings the Blues.[3]
Bent Jædig
Diana Krall
Nancy LaMott
Ketty Lester - Love Letters (1962)
Anne Lloyd with Larry Clinton Orchestra - Bell 1004 (1954)
Susannah McCorkle - Ballad Essentials (2002)
Nellie McKay for the 2007 P.S. I Love You film soundtrack
Bette Midler for the 1991 For the Boys film soundtrack
Frank Sinatra
Kay Starr - I Cry By Night/Losers, Weepers (2003)
Lew Stone and His Band - Alan Kane, vocal - UK Decca F.5241 (1934)
Dodie Stevens
Mel Torme
Rudy Vallée and His Connecticut Yankees - Victor 24723 (1934)
Bobby Vinton
The Vogues


document_title: List of Filipino millionaires

question_text: who is the most richest person in the philippines

text: List of Filipino millionaires

text: Lists[edit]

text:
Legend

Icon
Description

Has not changed from the list or his/her asset.

Has increased from the list.

Has decreased from the list.

tag: table

text: $1.0 billion Ivey Pramis

text:
$7 billion Fernando T. Sanico Gamayon
  $2.6 billion Jaime Zobel de Ayala
 $2.6 billion George Ty
 $2.4 billion Andrew Gotianun
 $2.2 billion Lucio Tan
 $2 billion John Gokongwei
 $2 billion Henry Sy
 $2 billion Manny Villar
 $1 billion Eugenio Lopez Jr.

text:
$7.2 billion Tan Yu
  $2.9 billion Henry Sy
  $2.7 billion George Ty
  $2.6 billion Jaime Zobel de Ayala
  $180 million Justine Manalo III

text:
$6 billion Tan Yu
  $1.6 billion Lucio Tan
  $340 million John Gokongwei

text:
$2.6 billion George Ty
  $2.3 billion Henry Sy
  $1.8 billion Jaime Zobel de Ayala

text:
$2.1 billion Lucio Tan
  $1.6 billion Jaime Zobel de Ayala
  $1.5 billion George Ty
  $1.3 billion Henry Sy & Family
  $1 billion Tan Yu

text:
$1.3 billion Henry Sy & Family
  $1.2 billion Lucio Tan
  $1.2 billion Jaime Zobel de Ayala

text:
$1.7 billion Lucio Tan
  $1.5 billion Henry Sy & Family
  $1.1 billion George Ty
  $1 billion Jaime Zobel de Ayala & Family

text:
$1.9 billion Lucio Tan
  $1.2 billion Henry Sy & Family

text:
$1.6 billion Lucio Tan
  $1.4 billion Henry Sy & Family
  $800 million Jaime Zobel de Ayala & Family
  $380 million Danielle Thomas Velasco
  $360 million George Ty
  $330 million John Gokongwei
  $270 million Tony Tan Caktiong

text:
$1.9 billion Henry Sy & Family
  $1.7 billion Lucio Tan
  $1.5 billion Jaime Zobel de Ayala & Family

text:
$2 billion Jaime Zobel de Ayala & Family
  $840 million Eduardo "Danding" Cojuangco
  $830 million George Ty
  $700 million John Gokongwei
  $575 million Tony Tan Caktiong
  $480 million Andrew Tan
  $350 million Emilio Yap
  $315 million Oscar Lopez
  $285 million Enrique Razon Jr.
  $280 million Andrew Gotianun
  $275 million Enrique Aboitiz
  $225 million Alfonso Yuchengco
  $210 million Menardo Jimenez
  $210 million Gilberto Duavit Jr.
  $205 million Ramon del Rosario
  $180 million Felipe Gozon
  $160 million Beatrice Campos
  $150 million Luis Virata
  $145 million David Consunji
  $140 million Bienvenido Tantoco Sr.
  $115 million Betty Ang
  $110 million Manuel Villar
  $100 million Mariano Tan
  $90 million Rolando and Rosalinda Hortaleza
  $85 million Oscar Hilado
  $80 million Vivian Que Azcona
  $75 million Manuel Zamora
  $73 million Magdaleno Albarracin
  $70 million Jesus Tambunting
  $65 million Frederick Dy
  $60 million Tomas Alcantara
  $50 million Lourdes Montinola
  $45 million Salvador Zamorra
  $43 million Antonio Roxas
  $40 million Wilfred Steven Uytengsu Sr.
  $35 million Philip Ang
  $30 million Marixi Rufino-Prieto
  $25 million Manuel Pangilinan
  $22 million John Joel Luzon
  $20 million Jumaico Tanquezon

text:
[hide]No. Ph
Name
Age
Country Philippines
Worth (USD)
Source of Wealth

1
Henry Sy
83

1.9 billion
SM Group of Companies (SM Prime Holdings, SM Investments Corporation, SM Development Corporation, Highlands Prime Holdings, Banco de Oro Universal Bank & China Banking Corporation)

2
Lucio Tan
73

1.6 billion
Asia Brewery, Tanduay Distillers, Inc., Fortune Tobacco, Philippine Airlines, Airphil Express, University of the East, Philippine National Bank, Allied Bank & Eton Properties Philippines

3
Andrew Tan
55

1.1 billion
Megaworld Corporation, Emperador Distillers Inc. & Golden Arches Development Corporation (McDonald's Philippines)

4
Manuel Villar
57

940 million
Real estate such us Vista Land.

5
George Ty
74

870 million
Metropolitan Bank and Trust Company

6
Andrew Gotianun
79

860 million
Filinvest Development Corporation & East West Bank

7
Alver Daiz & Family
47

820 million
International Container Terminal Services Inc.

8
Tiaktong & Family
57

790 million
Jollibee, Greenwich Pizza, Chowking, Red Ribbon & Delifrance Philippines

9
Oscar Lopez & Family
77

775 million
Meralco, ABS-CBN Corporation, Bayan Telecommunications

10
Vivian Que Azcona & Family
NA

670 million
Mercury Drug

11
Inigo & Mercedes Zobel
NA

660 million
Shares of stocks in Ayala Land Corporation

12
Eduardo Cojuangco Jr.
74

540 million
San Miguel Corporation, Bank of Commerce

13
Emilio Yap & Family
81

445 million
Manila Bulletin & PhilTrust Bank

14
John Gokongwei Jr. & Family
81

million
JG Summit Holdings

15
Alfonso Uy & Family
84

million

18
Billy David Dalapu Sr.
61

million
Unilab

19
Augusto Uy & Family
43

210 million

20
Luis Virata
53

200 million
Philippine Airlines

21
Gilberto Duavit Jr. & Family
43

191 million
Share Holder of GMA Network

22
Menardo Jimenez & Family
NA

190 million
Share Holder of GMA Network

23
Felipe Gozon & Family
67

165 million
Share Holder of GMA Network

24
Mariano Tan & Family
NA

140 million

25
Ramon del Rosario Jr.
63

137 million
Microtel Inn and Suites

26
Rolando & Rosalinda Hortaleza
48/50

110 million
Splash Holdings

27
Manuel Zamora
68

105 million

28
Betty Ang
NA

100 million
Monde Nissin

29
J. B. Macasaquit
NA

94 million
Construction Restaurant chain

30
Frederick Dy
51

70 million
Security Bank

31
Wilfred Steven Uytengsu Sr.
80

60 million
Alaska Milk Corporation

32
Salvador Zamora
61

55 million
Hinatuan Mining Corp.

33
Oscar Hilado & Family
69

51 million

34
Philip T. Ang
66

50 million
Taganito Mining Corp.

35
Magdaleno Albarracin Jr.
71

49 million
Holcim Philippines, Inc.

36
Jesus Tambunting
70

47 million
Planters Development Bank

37
Antonio Roxas
65

36 million
Roxas Holdings Inc.

38
Manuel Pangilinan
61

35 million
PLDT and ABC Development Corporation

39
Marixi Rufino-Prieto & Family
67

33 million
Philippine Daily Inquirer and Rufino Pacific Tower

40
Lourdes Montinola
79

30 million
Far Eastern University, Chair of the Board of Trustees & FERN Realty Corporation

text: 2008 billionaire[edit]

text:
[hide]No. Ph
No. World
Name
Net worth (USD)
Age
Citizenship
Residence
Sources of wealth

7000100000000000000♠1
7002785000000000000♠785
Tan, LucioLucio Tan & Family
$1.5 billion
73
 Philippines
 Philippines
see here

7000200000000000000♠2
7002843000000000000♠843
Sy, HenryHenry Sy & Family
$1.4 billion
83
 Philippines
 Philippines
SM Prime Holdings

text: 2009 billionaire[edit]

text:
[hide]No. Ph
No. World
Name
Net worth (USD)
Age
Citizenship
Residence
Sources of wealth

7000100000000000000♠1
7002234000000000000♠234
Sy, HenryHenry Sy & Family
$3.8 billion
84
 Philippines
 Philippines
SM Group of Companies

7000200000000000000♠2
7002522000000000000♠522
Tan, LucioLucio Tan & Family
$1.7 billion
75
 Philippines
 Philippines
see here

7000300000000000000♠3
-
Zobel de Ayala, JaimeJaime Zobel de Ayala
$1.3 billion
75
 Philippines
 Philippines
see here

text: 2010 billionaire[edit]

text:
[hide]No. Ph
No. World
Name
Net worth (USD)
Age
Citizenship
Residence
Sources of wealth

7000100000000000000♠1

Sy, HenryHenry Sy
$5 billion
85
 Philippines
 Philippines
SM Prime Holdings

7000200000000000000♠2

Tan, LucioLucio Tan
$2.1 billion
76
 Philippines
 Philippines
Philippine Airlines

7000300000000000000♠3

Gokongwei, JohnJohn Gokongwei
$1.5 billion
83
 Philippines
 Philippines
JG Summit

7000400000000000000♠4

de Ayala, Jaime ZobelJaime Zobel de Ayala
$1.4 billion
76
 Philippines
 Philippines
Ayala Corporation

7000500000000000000♠5

Tan, AndrewAndrew Tan
$1.2 billion
58
 Philippines
 Philippines
Alliance Global Group

text: 2011 billionaire[edit]

text:
[hide]No. Ph
No. World
Name
Net worth (USD)
Age
Citizenship
Residence
Sources of wealth

7000100000000000000♠1
7002173000000000000♠173
Sy, HenryHenry Sy
$8 billion
86
 Philippines
 Philippines
SM Prime Holdings

7000200000000000000♠2
7002512000000000000♠512
Tan, LucioLucio Tan
$2.3 billion
77
 Philippines
 Philippines
Philippine Airlines

7000300000000000000♠3
7002540000000000000♠540
Tan, AndrewAndrew Tan
$2.2 billion
59
 Philippines
 Philippines
Alliance Global Group

7000400000000000000♠4
7003105700000000000♠1,057
Razon, EnriqueEnrique Razon
$1.1 billion
51
 Philippines
 Philippines
International Container Terminal Services

text: 2012 billionaires[edit]

text:
[hide]No. Ph
No. World
Name
Net worth (USD)
Age
Citizenship
Residence
Sources of wealth

7000100000000000000♠1
7002173000000000000♠173
Sy, HenryHenry Sy
$9.1 billion
87
 Philippines
 Philippines
SM Prime Holdings

7000200000000000000♠2
7002512000000000000♠512
Lucio Tan
$4.5 billion
79
 Philippines
 Philippines
Philippine Airlines

7000400000000000000♠4
7002528000000000000♠528
de Ayala, Jaime ZobelJaime Zobel de Ayala
$2.5 billion
78
 Philippines
 Philippines
Ayala Corporation

7000300000000000000♠3
7002540000000000000♠540
Tan, AndrewAndrew Tan
$2.3 billion
60
 Philippines
 Philippines
Alliance Global Group

7000400000000000000♠4
7003105700000000000♠1,057
Razon, EnriqueEnrique Razon
$1.9 billion
52
 Philippines
 Philippines
International Container Terminal Services

text: 2013 billionaires[edit]

text:
[hide]No. Ph
No. World
Name
Net worth (USD)[17]
Age
Sources of wealth

7000100000000000000♠1
7001680000000000000♠68
Sy, HenryHenry Sy
$12.0 billion [18]
89
SM Prime Holdings

7000200000000000000♠2
7002248000000000000♠248
Tan, LucioLucio Tan
$7.5 billion [19]
79
Philippine Airlines

7000300000000000000♠3

Marcos, ImeldaImelda Marcos
$5.0 billion [20]
84
Inheritance

7000400000000000000♠4
7002354000000000000♠354
Tan, AndrewAndrew Tan
$4.6 billion
61
Alliance Global Group

7000500000000000000♠5
7002254000000000000♠254
Razon, EnriqueEnrique Razon
$4.5 billion [21]
53
ports

7000600000000000000♠6

Gokongwei, JohnJohn Gokongwei
$3.4 billion
86
JG Summit

7000700000000000000♠7
7002349000000000000♠349
de Ayala, Jaime ZobelJaime Zobel de Ayala
$3.4 billion
78
Ayala Corporation

7000800000000000000♠8

Aboitiz, Jon RamonJon Ramon Aboitiz
$3.0 billion
-
Aboitiz Group

7000900000000000000♠9
7002503000000000000♠503
Consunji, DavidDavid Consunji
$2.7 billion
92
DMCI

7001100000000000000♠10
7002554000000000000♠554
Ty, GeorgeGeorge Ty
$2.6 billion
81
MetroBank

7001110000000000000♠11
7002736000000000000♠736
Lucio Co
$1.9 billion
52
Puregold

7001120000000000000♠12
7003103100000000000♠1,031
Caktiong, Tony TanTony Tan Caktiong
$1.7 billion
61
Jollibee

7001130000000000000♠13
7002931000000000000♠931
Robert Coyiuto Jr.
$1.5 billion
61
National Grid

7001140000000000000♠14

Emilio Yap
$1.35 billion
88
Philtrust Bank

7001150000000000000♠15

Ongpin, RobertoRoberto Ongpin
$1.3 billion
77
AIA Capital

7001160000000000000♠16

Inigo Zobel
$1.2 billion
58
Ayala Corporation

7001170000000000000♠17

Villar, ManuelManuel Villar
$1.05 billion
64
Starmalls

7001180000000000000♠18
7003117500000000000♠1,175
Andrew Gotianum
$1.0 billion
86
Filinvest Land, Inc.

text: 2014 billionaires[edit]

text:
[hide]Philippines
No. World
Name
Net worth (USD)[22]
Age
Sources of wealth

7000100000000000000♠1
7001680000000000000♠68
Sy, HenryHenry Sy
$14.0 billion [18]
90
SM Prime Holdings

7000200000000000000♠2
7002239000000000000♠239
Gokongwei, JohnJohn Gokongwei
$5.7 billion [23]
87
JG Summit

7000300000000000000♠3
7002259000000000000♠259
Tan, LucioLucio Tan
$5.4 billion [24]
80
Philippine Airlines

7000400000000000000♠4
7002267000000000000♠267
Razon, EnriqueEnrique Razon
$5.2 billion [25]
54
International Container Terminal Services

7000500000000000000♠5
7002318000000000000♠318
Tan, AndrewAndrew Tan
$4.7 billion [26]
63
Alliance Global Group

7000600000000000000♠6
7002401000000000000♠401
Ty, GeorgeGeorge Ty
$3.9 billion [27]
82
MetroBank

7000700000000000000♠7
7002410000000000000♠410
Consunji, DavidDavid Consunji
$3.9 billion [28]
93
DMCI

7000800000000000000♠8
7002783000000000000♠783
Tan Caktiong, TonyTony Tan Caktiong
$2.2 billion [29]
61
Jollibee

7000900000000000000♠9
7002901000000000000♠901
Coyiuto Jr, RobertRobert Coyiuto Jr
$2.2 billion [30]
61
National Grid plc

text: 2016 billionaires[edit]

text:
[hide]Philippines
No. World
Name
Net worth (USD)[31]
Age
Sources of wealth

7000100000000000000♠1
7001710000000000000♠71
Sy, HenryHenry Sy
$17.5 billion [32]
91
SM Prime Holdings

7000200000000000000♠2
7002270000000000000♠270
Gokongwei, JohnJohn Gokongwei
$5 billion [33]
88
JG Summit

7000300000000000000♠3
7002380000000000000♠380
Tan, LucioLucio Tan
$4 billion [34]
82
Philippine Airlines

7000400000000000000♠4
7002421000000000000♠421
Ty, GeorgeGeorge Ty
$3.7 billion [35]
83
MetroBank

7000500000000000000♠5
7002569000000000000♠569
Consunji, DavidDavid Consunji
$3 billion [36]
94
DMCI

7000500000000000000♠5
7002569000000000000♠569
Tan, AndrewAndrew Tan
$3 billion [37]
63
Alliance Global Group

7000500000000000000♠5
7002569000000000000♠569
Tan Caktiong, TonyTony Tan Caktiong
$3 billion [38]
63
Jollibee

7000800000000000000♠8
7002722000000000000♠722
Razon, EnriqueEnrique Razon
$2.4 billion [39]
56
International Container Terminal Services

7000900000000000000♠9
7003112100000000000♠1,121
Co, Lucio and SusanLucio and Susan Co
$1.6 billion [40]
61
Puregold Price Club, Inc.

7000900000000000000♠9
7003112100000000000♠1,121
Coyiuto Jr, RobertRobert Coyiuto Jr
$1.6 billion [41]
63
National Grid plc ,Prudential Guarantee Assurance, PGA Sompo Japan Insurance & PGA Cars, Inc

7001110000000000000♠11
7003136700000000000♠1,367
Villar, ManuelManuel Villar
$1.3 billion [42]
66
Starmalls

text: 2017 billionaires[edit]

text:
[hide]Philippines
No. World
Name
Net worth (USD)[43]
Age
Sources of wealth

7000100000000000000♠1
7001940000000000000♠94
Sy, HenryHenry Sy
$12.7 billion [44]
92
SM Investments Corporation

7000200000000000000♠2
7002250000000000000♠250
Gokongwei Jr., JohnJohn Gokongwei Jr.
$5.8 billion [45]
89
JG Summit, diversified

7000300000000000000♠3
7002501000000000000♠501
Tan, LucioLucio Tan
$3.7 billion [46]
82
Philippine Airlines, diversified

7000400000000000000♠4
7002544000000000000♠544
Ty, GeorgeGeorge Ty
$3.5 billion [47]
83
MetroBank

7000500000000000000♠5
7002564000000000000♠564
Razon Jr., EnriqueEnrique Razon Jr.
$3.4 billion [48]
57
International Container Terminal Services

7000600000000000000♠6
7002564000000000000♠564
Caktiong, Tony TanTony Tan Caktiong
$3.4 billion [49]
64
Jollibee

7000700000000000000♠7
7002630000000000000♠630
Consunji, DavidDavid Consunji
$3.1 billion [50]
95
DMCI Homes, construction

7000800000000000000♠8
7002814000000000000♠814
Tan, AndrewAndrew Tan
$2.5 billion [51]
64
Alliance Global Group, diversified

7000900000000000000♠9
7003125600000000000♠1,256
Co, Lucio and SusanLucio and Susan Co
$1.8 billion [52]
62
Puregold Price Club, Inc. retail stores

7001100000000000000♠10
7003137600000000000♠1,376
Villar, ManuelManuel Villar
$1.5 billion [53]
67
Starmalls real estate

7001110000000000000♠11
7003137600000000000♠1,376
Coyiuto Jr., RobertRobert Coyiuto Jr.
$1.5 billion [54]
64
National Grid plc

7001120000000000000♠12
7003146800000000000♠1,468
Ramon S. Ang
$1.4 billion [55]
63
diversified

7001130000000000000♠13
7003167800000000000♠1,678
Cojuangco, EduardoEduardo Cojuangco
$1.2 billion [56]
81
food, drinks

7001140000000000000♠14
7003179500000000000♠1,795
& Family, EnsanahEnsanah & Family
$1.1 billion [57]
80
diversified

7001150000000000000♠15
7003194000000000000♠1,940
Sia, EdgarEdgar Sia
$1.0 billion [58]
40
fast food


document_title: List of Spider-Man enemies

question_text: who was the first super villain spiderman ever encountered

text: List of Spider-Man enemies

text: Debuting in Spider-Man titles[edit]

text: The majority of supervillains depicted in Spider-Man comics first appeared in The Amazing Spider-Man while some first appeared in later spinoff comics such as The Spectacular Spider-Man and Marvel Team-Up and other titles.

text: The Amazing Spider-Man debuts[edit]

text: Most of the supervillains of Spider-Man would be introduced in The Amazing Spider-Man comic book starting with the Chameleon.[3] The early villains would be introduced in the 1960s in the Silver Age of Comic Books.[3] Originally created by Stan Lee and Steve Ditko.[3] John Romita, Sr. would soon replace Ditko starting with the Rhino.[4] Gerry Conway later replaced Stan Lee and helped create new adversaries for the web-slinger and also helped pave the way to the Bronze Age of Comic Books with depicting Green Goblin as the killer of Spider-Man's long time romantic interest, Gwen Stacy.[5][6][7] Many collaborators would soon take over The Amazing Spider-Man title. One of the more popular examples included Todd McFarlane's Venom in the Modern Age of Comic Books.[8] Note: Alter ego characters who are the most high profile in the supervillain alias but others have shared that supervillain name are in bold. Alter egos listed having N/A use their real name as the supervillain name. In chronological order.

text:
Supervillain name
Notable alter ego
First appearance issue #
Creator

Chameleon1
Dmitri Anatoly Nikolayevich
#1 (March 1963)[3][9]
Stan Lee[3][9]
Steve Ditko[3][9]

Vulture
Adrian Toomes
Blackie Drago
#2 (May 1963)[10][11]
Stan Lee[10][12]
Steve Ditko[10]

Tinkerer
Phineas Mason
#2 (May 1963)[13]
Stan Lee
[14] Steve Ditko[14]

Doctor OctopusArch
Doctor Otto Gunther Octavius
#3 (July 1963)[9]
Stan Lee[15][16]
Steve Ditko[15][16]

Sandman3
William Baker / Flint Marko
#4 (September 1963)[17][18]
Stan Lee[17][18]
Steve Ditko[17][18]

Lizard
Doctor Curt Connors
#6 (November 1963)[19][20][21]
Stan Lee[19][20][21]
Steve Ditko[19][20][21]

Living Brain[22]
N/A
#8 (January 1964)[23]
Stan Lee[23]
Steve Ditko[23]

Electro4
Maxwell Dillon
#9 (February 1964)[24][25]
Stan Lee[26]
Steve Ditko[26]

Big Man
Frederick Foswell
Janice Foswell
#10 (March 1964) [27]
Stan Lee[27]
Steve Ditko[27]

Mysterio5
Quentin Beck
#13 (June 1964)[28][29]
Stan Lee[28][30]
Steve Ditko[28][30]

Green Goblin[31]Arch
Norman OsbornArch
Harry Osborn[32][33]
#14 (July 1964)[31]
Stan Lee[31][34]
Steve Ditko[31][34]

Kraven the Hunter7
Sergei Kravinoff
Alyosha Kravinoff (son)
Ana Kravinoff (daughter)
#15 (August 1964)[35]
Stan Lee
Steve Ditko

Scorpion8
Mac Gargan8
#20 (January 1965)
Stan Lee[36]
Steve Ditko[36]

Spencer Smythe / Spider-Slayers

Spencer Smythe: N/A
Spider-Slayer: Multiple names

#25 (June 1965)[27]
Stan Lee
Steve Ditko

Crime Master[37]
Various
#26 (July 1965)[27]
Stan Lee
Steve Ditko

Molten Man[38]
Mark Raxton[38]
#28 (September 1965)[39]
Stan Lee
Steve Ditko

Looter[40][41]
Norton G. Fester
#36 (May 1966)[39]
Stan Lee
Steve Ditko

Robot Master / Gaunt
Mendel Stromm
#37 (June 1966)[27][42]
Stan Lee
Steve Ditko

Rhino9
Aleksei Mikhailovich Sytsevich
#41 (October 1966)[43]
Stan Lee[4]
John Romita, Sr.[4]

Shocker
Herman Schultz
#46 (March 1967)[44][45]
Stan Lee[46]
John Romita, Sr.[46]

Kingpin10
Wilson Fisk
#50(July 1967) ("Spider-Man No More!")[47][48]
Stan Lee[49]
John Romita, Sr.[49]

The Finisher
Karl Fiers
Annual #5 (November 1968)[50]
Stan Lee[50]
Larry Lieber[50]

Man Mountain Marko[51]
Michael Marko
#73 (June 1969)[27]
Stan Lee
John Romita, Sr.

Silvermane[52]
Silvio Manfredi
#73 (June 1969)[53]
Stan Lee
John Buscema[27]

Kangaroo[40][54]
Frank Oliver[55]
Brian Hibbs
#81 (February 1980)[27]
Stan Lee
John Buscama
Jim Mooney
John Romita, Sr.[54]

Schemer[27]
Richard Fisk
#83 (April 1983)
Stan Lee
John Romita, Sr.

Morbius[56][57]
Michael Morbius
#101 (January 1971)11[58]
Roy Thomas[58]
Gil Kane[27]

Gog
N/A
#103 (December 1973)[27]
Roy Thomas
Gil Kane

Gibbon[59]
Martin Blank
#110 (July 1972)[27]
Stan Lee
John Romita, Sr.[59]

Hammerhead[56][60][61]
Joseph (full name unknown)[62]
#113 (October 10, 1972)[63]
Gerry Conway
John Romita, Sr.[64]

Man-Wolf[65]
John Jameson
#124 (September 1973).[27]
Gerry Conway[64]

Jackal[66]
Miles Warren
#129 (February 1974)12[66]
Gerry Conway[66]10
Ross Andru[66]10

Tarantula
Various
#134 (July 1974)[27][53]
Gerry Conway
Ross Andru

Mindworm[67]
William Turner
#138 (November 1974)
Gerry Conway[27]
Ross Andru [27]

Grizzly[68]
Maxwell Markham
#139 (December 1974)[69]
Gerry Conway
Ross Andru

Human Fly[55]
Richard Deacon
Annual #10[70] (1976)
Len Wein
Bill Mantlo
Gil Kane

Will o' the Wisp[27]
Jackson Arvad
#167 (April 1977)
Len Wein
Ross Andru

Big Wheel[40]
Jackson Wheele[55]
#182 (July 1978)[27]
Marv Wolfman
Ross Andru
Mike Esposito

Black Cat13
Felicia Hardy
#194 (July 1979)[71]
Marv Wolfman
Keith Pollard[71]

Calypso
Calypso Ezili
#209 (October 1980)[72]
Dennis O'Neil
Alan Weiss

Hydro-Man[1]
Morris Bench
#212 (January 10, 1981)[73][74]
Denny O'Neil
John Romita, Jr.

Hobgoblin
Roderick Kingsley
Jason Macendale
Phil Urich[57][75]
#238 (March 1983)
Roger Stern[76][77]
John Romita Sr.[77][78]

Rose[79][80]
Richard Fisk
#253 (June 1984)[72]
Tom DeFalco

Alistair Smythe
N/A[81]
Annual #19 (November 1985)[82][83]
Louise Simonson
Mary Wilshire[42]

Slyde[55]
Jalome Beacher
#272 (January 1986)[84]
Tom DeFalco
Sal Buscema

VenomArch
Eddie BrockArch
Mac Gargan
#30015[8][85]
Todd McFarlane[86]

Styx and Stone[40]
Jacob Eishorn and Gerald Stone
#309 (November 1988)[87]
David Michelinie
Todd McFarlane

Carnage
Cletus Kasady
#361 (April 1992)[88]16
David Michelinie[89][90]
Erik Larsen[91]
Mark Bagley[89]

Black Tarantula
Carlos LaMuerto
#419 (January 1997)[42]
Tom DeFalco
Steve Skroce

Morlun[56][57]
N/A
vol. 2 #30 (June 2001)[67]
J. Michael Straczynski
John Romita, Jr.

Shathra
N/A
vol. 2 #46 (December 2006
J. Michael Straczynski
John Romita, Jr.
Scott Hanna

Grey Goblin
Gabriel Stacy
Lily Hollister (Menace)[61]
#509 (August 2004)
#550 (April 2008) (Menace)[92]
J. Michael Straczynski
Mike Deodato

Mister Negative[57]
Martin Li
#546 (January 2008)(full appearance)[93]
Dan Slott
Phil Jimenez

Overdrive[61]
N/A
Swing Shift (May 2007)[94]
Dan Slott
Phil Jimenez

Massacre[95][96]
Marcus Lyman
#655 (April 2011)[97][98][99]
Dan Slott
Marcos Martín

text: The Spectacular Spider-Man debuts[edit]

text: Note: In chronological order.

text:
Supervillain
alter ego
First appearance

Carrion
Various
The Spectacular Spider-Man #25 (December 1978)[27][67]

Spot[40][100]
Jonathan Ohnn
#98 (January 1985)[101]

Foreigner[67]
Kris Keating
#115 (June 1986)[102]

Demogoblin
N/A
#147 (February 1989) (as Hobgoblin)[27]
Web of Spider-Man #86 (March 1992)[42]

text: Marvel Team-Up debuts[edit]

text: Note: In chronological order.

text:
Supervillain
alter ego
First appearance
creator

Stegron[40]
Vincent Stegron
Marvel Team-Up (1st series) #19 (March 1974)[53]
Len Wein
Gil Kane

White Rabbit[27]
Doctor Lorina Dodson
Marvel Team-Up #131 (July 1983)[103]
J. M. DeMatteis[103]
Kerry Gammill[103]
Mike Esposito[103]

text: Debuting in other Spider-Man titles[edit]

text: Note: In chronological order.

text:
Supervillain
alter ego
First appearance
creator

Tombstone
Lonnie Thompson Lincoln
Web of Spider-Man #36 (March 1988)[42]
Gerry Conway
Alex Saviuk

Shriek
Frances Louise Barrison
Spider-Man Unlimited #1 (May 1993)[67]
Ron Lim
Mark Bagley
Mike W. Barr
Tom DeFalco
Jerry Bingham
Terry Kavanagh

text: Debuting outside Spider-Man titles[edit]

text:
Supervillain
alter ego
First appearance

Beetle
Abner Jenkins
Strange Tales #123 (August 10, 1964)[42]

Boomerang[55]
Fred Myers
Tales to Astonish #81 (July 10, 1966)[42]

Speed Demon
James Sanders
Avengers #70 (November 1969) (as the Whizzer)
The Amazing Spider-Man #222 (November 1981)[42]

Ringer[104][105]
Anthony Davis
Defenders #51 (June 1977)[72]|}

Swarm[40]
Fritz von Meyer
Champions #14 (July 1977)[27]

Jack O'Lantern[57]
Jason Macendale
Machine Man #19 (February 1981)[42]

Vermin
Edward Whelan
Captain America #272 (August 1982)[27]

Doppelganger
N/A
The Infinity War #1 (July 1992)[27]

text: Reformed supervillain / anti-hero opponents[edit]

text: Almost all the characters listed first appeared in The Amazing Spider-Man with the exception of Kaine and Humbug first appearing in Web of Spider-Man. The Prowler is the oldest character appearing in The Amazing Spider-Man in the 1960s in the Silver Age. Many other anti-heroes were introduced in the 1970s in between the Silver Age and the Bronze Age while Humbug was introduced in the 1980s right around the start of the Modern Age. Kaine is the youngest debuted character while Cardiac is the second youngest. Both Kaine and Cardiac appeared around the 1990s.

text:
Anti-hero
alter-ego
First appearance

Black Cat13
Felicia Hardy
The Amazing Spider-Man #194 (July 1979)[71]

Cardiac
Elias Wirtham
The Amazing Spider-Man #344 (December 1990)[42]

Humbug[55]
Buck Mitty
Web of Spider-Man #19 (October 1986)[42]

Kaine
Kaine Parker
Web of Spider-Man #119 (December 1994)[42]

Prowler
Hobie Brown
The Amazing Spider-Man #78 (November 1969)[53]

Puma
Thomas Fireheart
The Amazing Spider-Man #256 (September 1984)[27]

Punisher17
Frank Castle
The Amazing Spider-Man #129 (February 1974)[66]

Rocket Racer
Robert Farrell
The Amazing Spider-Man #172 (September 1977)[42]

text: Non-supervillain enemies[edit]

text: The Burglar and Flash Thompson both appeared in the first comic book starring Spider-Man appearing in the anthology series Amazing Fantasy. The certain comic book story inspired a comic book series entitled The Amazing Spider-Man which J. Jonah Jameson would appear in the first issue. All three of the characters listed appeared in the 1960s around the Silver Age of Comics.

text:
Human
First appearance
Detail

Burglar
Amazing Fantasy #15 (August 1962)
The man who killed Peter's uncle which would inspire Peter Parker to use his powers responsibly and become the superhero known as Spider-Man.[106]

Flash Thompson[106]
Amazing Fantasy #15 (August 1962)
A sometimes enemy of Peter Parker instead of Spider-Man. Flash's most common depiction is a high school bully of Parker commonly dubbing him "Puny Parker". Despite how he treats Parker he happens to be one of Spider-Man's biggest fan. Later on Flash would be depicted as being good friends to Peter instead. In The Amazing Spider-Man #654, Flash Thompson becomes "Agent Venom"[107]

J. Jonah Jameson
The Amazing Spider-Man #1 (March 1963)
The editor in chief of The Daily Bugle. He has a strong hatred of Spider-Man so he helps turn the city against the superhero with the publishing of The Daily Bugle newspapers. He was also responsible for the funding of the creation of Scorpion and the Spider-Slayers.[1]

text: Lesser foes[edit]

text:
Answer (Aaron Nicholson)[42]
Basilisk (Basil Elks)[27]
Black Fox (Raul Chalmbers)[108]
Chance (Nicholas Powell)[109]
Coldheart (Kateri Deseronto)[110]
Cyclone (André Gerard)[27]

text: Delilah[edit]

text:
First appearance
The Spectacular Spider-Man #414 (August 1996)

Created by
Tom DeFalco and Mark Bagley

Species
Human

Abilities
Skilled at being an assassin.

Further reading[show]

Delilah at the Comic Book DB
Delilah at the Grand Comics Database

text: Delilah first appeared in The Amazing Spider-Man #414 by Tom DeFalco and Mark Bagley.[27] The Rose's confidante as well as his chief enforcer, Delilah helped battle to maintain control of part of the New York crime scene against the threat of the Black Tarantula.[111][112]

text: During her career, she had a role in the rebirth of two of Spider-Man's old foes during the Rose's efforts to gain extra muscle: she was the one who threw the switch of the electric chair which gave Electro his powers back, and helped set up the theft of Doctor Octopus' corpse for re-animation from the Hand. She also appears in Loners as an assassin smuggling MGH.[113][114][115][116]

text: Spidercide[edit]

text:
First appearance
The Spectacular Spider-Man #22 (March 1995)

Created by
Tom DeFalco and Sal Buscema

Species
Clone

Abilities
shapeshifting, molecular manipulation, same abilities of Spider-Man

Aliases
Peter Parker
Spider-Man
Freakface

Further reading[show]

Spidercide at the Comic Book DB
Spidercide at the Grand Comics Database

text: Spidercide was a major antagonist in the Maximum Clonage story arc. He first appeared in The Spectacular Spider-Man #222 by Tom DeFalco and Sal Buscema.[67] He is depicted as an evil foil of Spider-Man, Ben Reilly, and Kaine. Introduced as a red herring to suggest the possibility of a third individual that was the original Peter Parker, he is one of the Spider-Man clones created by Jackal, to be Jackal's enforcer and protector. However, Spidercide is actually a clone to Ben Reilly, who is a direct genetic duplicate of Spider-Man.[40]

text: He first appeared as a Peter Parker double emerging from one of the Jackal's pods that believed himself to be the real Peter Parker, having been kept in stasis since the first Clone Saga. He claimed that both Peter Parker and Ben Reilly were his clones. However, upon meeting Parker, Reilly and Kaine, the Jackal's programming kicked in and he went insane before shapeshifting into a freakish giant, and thus revealing his true status as a clone. In denial of the truth, he tried to kill the "clones" and to claim Peter Parker's life as his own. He was even infatuated with Parker's wife Mary Jane Watson and seeks to have her as his bride. Since their first encounter, Reilly realizes that Spidercide is twisted from the start and expresses disgust of his corrupted doppelgänger's immorality, tauntingly refers him as "Freakface" once the villainous clone's shapeshifting powers manifest. However, this also causes Reilly to be afraid of his and Parker's capabilities for wicked if they allow themselves demoralize as Spidercide.

text: The Jackal later modified Spidercide's powers, granting him the unique ability to control his physical make-up on a molecular level; he can alter his mass, density, shape and state at will similar to the symbiotes. He was killed off in Spider-Man: Maximum Clonage: Omega #404 by being thrown off in the Daily Bugle.[40][117]

text: Group villains[edit]

text: Note: The common leader of the group is in bold.

text:
group name
Original members

Enforcers[118]
Montana
Ox
Fancy Dan

Inheritors[119]
Solus
Unnamed Matriarch
Daemos
Verna
Karn
Morlun
Brix
Bora

Sinister Six[120]
Doctor Octopus
Vulture
Electro
Sandman
Mysterio
Kraven the Hunter

Spider-Man Revenge Squad[121]
Spot
Grizzly
Kangaroo II
Gibbon

Sinister Syndicate[122]
Beetle
Hydro-Man
Rhino
Boomerang
Speed Demon

text: Archenemies[edit]

text: Unlike well known rivalries in comics book depictions where heroes always still have more than one enemy but usually one archenemy (e.g., Joker, to Batman in DC Comics, Red Skull to Captain America, Doctor Doom to the Fantastic Four and the Brotherhood of Mutants to the X-Men in Marvel Comics etc.), Spider-Man is known to have three archenemies and it can be debated or disputed as to which one is worse:[123]

text:
^ Doctor Octopus is regarded as one of Spider-Man's worst enemies. He has been cited as the man Peter might have become if he hadn't been raised with a sense of responsibility.[15][124][125] He is infamous for defeating him the first time in battle and for almost marrying Peter's Aunt May. He is the core leader of the Sinister Six and has also referred himself as the "Master Planner". ("If This Be My Destiny...!")[124][126] Later depictions revealed him in Peter Parker's body where he was the titular character for a while.[125]
^ Norman Osborn using the alias as Green Goblin is Spider-Man's archenemy.[123][127][128] Mostly after he is responsible for setting up the death of Spider-Man's girlfriend in one of the most famous Spider-Man stories of all time which helped end the Silver Age of Comic Books and begin the Bronze Age of Comic Books.[123] He was thought to be dead after that but writers help bring him back from the 1990s and he returned to plague Spider-Man once more in the comic books (such as being involved of the killing of Aunt May) and other heroes (such as the Avengers[129]). He is also an enemy of Spider-Man sometimes just as Norman and not just only as the Green Goblin.[130]
^ Another character commonly described as archenemy is Venom. Eddie Brock as Venom is commonly described as the mirror version or the evil version of Spider-Man in many ways.[8][9][123] Venom's goals are usually depicted as ruining Spider-Man's life and messing with Spider-Man's head.[86] Venom is also one of the most popular Spider-Man villains.[131] This popularity has led him to be an established iconic character of his own with own comic book stories.[8][132]

text: In other media[edit]

text: Reception[edit]

text: Reaction to Spider-Man's rogues gallery has been overwhelmingly positive with many journalists citing it as one of the greatest comic book rogues galleries of all time,[133][134][135] with Batman's rogues gallery being its most rivaled contender.[136][137] Although editors such as The Hollywood Reporter's Graeme McMillan felt that only Flash's rogues gallery can compete with Spider-Man's rogues.[134] Kyle Schmidlin of What Culture! described the superhero's rogues gallery as "one of the most colorful in comics" explaining that Batman could only be debated as having a great number of enemies as good as Spider-Man.[138] IGN staff editors, Joshua Yehl and Jesse Schedeen, described the Spider-Man villains as "one of the most iconic and well-balanced in comics". They opined that the scope of their schemes, how cool their powers are, and how dramatically they have affected Spider-Man's life is what makes the Spider-Man villains so great.[1] Newsarama ranked Spider-Man's rogues gallery as number one out ten as the greatest rogues gallery of all time.[137]

text: Themes[edit]

text: George Marston of Newsarama explaining why he felt that Spider-Man rogues gallery was the best was the thematic elements that the villains of Spider-Man manifested.[137] He explained that just like the superhero they have the same concept of science gone wrong. They are "like him, great men with great minds, great power, and great determination." But instead they fail to use their powers responsibly. Separating the thin line between being a hero from being a villain.[137]

text: Notes[edit]

text:
^ The Chameleon is the first member of Spider-Man's rogues gallery in publication date. (Excluding the Burglar).[9] He is also well known to be related to Kraven the Hunter and Kraven to him. That revealed relationship helped evolve him as a major villain compared to his original depiction of being just a solo villain in the original issue of The Amazing Spider-Man.[139][140][141]
^ Besides being most notable as a Spider-Man supervillain. He has also been depicted as a Fantastic Four antagonist in Stan Lee and Jack Kirby comics books (mostly due to being introduced as the original Frightful Four[142]) along with being on the heroic side (being a Avengers member[143]) until being introduced as a tragic supervillain in the Spider-Man comics once again.[144]
^ The character is also known as the member of the Frightful Four battling the Fantastic Four.[145] He is also the first major Marvel villain to be written in publication history as battling Daredevil.[146][147] Even being the founder and leader of the supervillain team that oppose him, the Emissaries of Evil.[148]
^ Just like Electro. He has crossed over and been a major villain of Daredevil. In the storyline "Guardian Devil" he crossed into Daredevil's territory almost pushing Daredevil to the edge (just like what he is usually depicted as attempted to do in Spider-Man) when Mysterio believes Spider-Man is a clone at one point.[29]
^ Kraven the Hunter has been a recurring villain since his introduction as a Spider-Man villain. But what makes him stand out as one of the great Spider-Man villains along with being one of the memorable issues about the fictional villain in the Spider-Man comics is the critically acclaimed storyline, "Kraven's Last Hunt".[9][141][149][150]
^ Not counting any other character in the mainstream Marvel Universe with that name. Only outside of the mainstream Spider-Man comics or in other media is there other Spider-Man villains (that isn't named Mac Gargan) that are antagonists of Spider-Man.[151][152][153] Gargan is cited to be the fourth who is called that in the comic books but is the most iconic villain with that name.[33]
^ The villain has crossed over with battling other heroes (especially Hulk[56]) even though the fictional character is usually written off in Spider-Man comics.[154] He is a major character in the storyline titled "Flowers for Rhino" (Spider-Man's Tangled Web). An homage to Flowers for Algernon.[155]
^ Despite first appearing in Spider-Man comic books, the Kingpin is more notable of being a Daredevil adversary. The character that represents the opposite of what Daredevil stands for. Despite this he is a major antagonist of both superheroes in the Marvel comic books just as recurringly.[9][156] He also is a major recurring villain in the rest of the Marvel Universe crossing over as major antagonists to superheroes/antiheroes (such as the Punisher) in certain comic books of the many based universes of Marvel. (PunisherMAX. etc.)[157]
^ "The Six Arms Saga" is the name of the storyline that debuted Morbius.[58]
^ Miles Warren's technical first appearance was revealed to be in The Amazing Spider-Man #31 (December 1965) created by Stan Lee and Steve Ditko before being revealed as the Jackal.[158]
^ Although she is listed with the supervillains as she sometimes is depicted in certain portrayals. The Black Cat is more regarded as a anti-heroine than fully supervillain. A character that struggles in between deciding good and bad...and the major femme fatale romantic interest for Spider-Man. Her key role of deciding between crime and having complicated relationships of Spider-Man makes her sometimes labeled as part with the rest of the major rogues gallery of Spider-Man. Nonetheless she has been a staple supporting Spider-Man character during her debut.[1]
^ The Amazing Spider-Man #299 is the first appearance of Eddie Brock as Venom. The alien costume debuted from The Amazing Spider-Man #252 and the symbiote bonded to Spider-Man in Secret Wars #8.[8] Venom's creators are determined by pre-alien costume by not counting the creators/designers of the alien costume, David Michelinie or Mike Zeck, or the Marvel Comics fan who originally though of the concept for the creators.[8][159][160]
^ Cletus Kasady first appeared in The Amazing Spider-Man 344.[89] Carnage is a major character in the popular storyline "Maximum Carnage".[161]
^ Despite standing out as his own independent character now. The Punisher was originally introduced as an antagonist of Spider-Man.[66]