Fibrous dysplasia is a mosaic disease that can involve any part or combination of the craniofacial, axillary, and/or appendicular skeleton. The type and severity of the complications therefore depend on the location and extent of the affected skeleton. The clinical spectrum is very broad, ranging from an isolated, asymptomatic monostotic lesion discovered incidentally, to severe disabling disease involving practically the entire skeleton and leading to loss of vision, hearing, and/or mobility.

Individual bone lesions typically manifest during the first few years of life and expand during childhood. The vast majority of clinically significant bone lesions are detectable by age 10 years, with few new and almost no clinically significant bone lesions appearing after age 15 years. Total body scintigraphy is useful to identify and determine the extent of bone lesions, and should be performed in all patients with suspected fibrous dysplasia.

Children with fibrous dysplasia in the appendicular skeleton typically present with limp, pain, and/or pathologic fractures. Frequent fractures and progressive deformity may lead to difficulties with ambulation and impaired mobility. In the craniofacial skeleton, fibrous dysplasia may present as a painless “lump” or facial asymmetry. Expansion of craniofacial lesions may lead to progressive facial deformity. In rare cases patients may develop vision and/or hearing loss due to compromise of the optic nerves and/or auditory canals, which is more common in patients with McCune-Albright syndrome associated growth hormone excess. Fibrous dysplasia commonly involves the spine, and may lead to scoliosis, which in rare instances may be severe. Untreated, progressive scoliosis is one of the few features of fibrous dysplasia that can lead to early fatality.

Bone pain is a common complication of fibrous dysplasia. It may present at any age, but most commonly develops during adolescence and progresses into adulthood.

Bone marrow stromal cells in fibrous dysplasia produce excess amounts of the phosphate-regulating hormone fibroblast growth factor-23 (FGF23), leading to loss of phosphate in the urine. Patients with hypophosphatemia may develop rickets/osteomalacia, increased fractures, and bone pain.

Despite this excess bone formation, people with osteopetrosis tend to have bones that are more brittle than normal. Mild osteopetrosis may cause no symptoms, and present no problems.

However, serious forms can result in...

- Stunted growth, deformity, and increased likelihood of fractures

- Patients suffer anemia, recurrent infections, and hepatosplenomegaly due to bone expansion leading to bone marrow narrowing and extramedullary hematopoiesis

- It can also result in blindness, facial paralysis, and deafness, due to the increased pressure put on the nerves by the extra bone

- Abnormal cortical bone morphology

- Abnormal form of the vertebral bodies

- Abnormality of temperature regulation

- Abnormality of the ribs

- Abnormality of vertebral epiphysis morphology

- Bone pain

- Cranial nerve paralysis

- Craniosynostosis

- Hearing impairment

- Hypocalcemia

Fibrous dysplasia is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment, and pain. Disease occurs along a broad clinical spectrum ranging from asymptomatic, incidental lesions to severe disabling disease. Disease can affect one bone (monostotic) or multiple (polyostotic), and may occur in isolation or in combination with cafe-au-lait skin macules and hyperfunctioning endocrinopathies, termed McCune-Albright syndrome. More rarely, fibrous dysplasia may be associated with intramuscular myxomas, termed Mazabraud's syndrome. Fibrous dysplasia is very rare, and there is no known cure. Fibrous dysplasia is not a form of cancer.

A pathologic fracture is a bone fracture caused by disease that led to weakness of the bone structure. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as: cancer, infection (such as osteomyelitis), inherited bone disorders, or a bone cyst. Only a small number of conditions are commonly responsible for pathological fractures, including osteoporosis, osteomalacia, Paget's disease, osteitis, osteogenesis imperfecta, benign bone tumours and cysts, secondary malignant bone tumours and primary malignant bone tumours.

Fragility fracture is a type of pathologic fracture that occurs as result of normal activities, such as a fall from standing height or less. There are three fracture sites said to be typical of fragility fractures: vertebral fractures, fractures of the neck of the femur, and Colles fracture of the wrist. This definition arises because a normal human being ought to be able to fall from standing height without breaking any bones, and a fracture therefore suggests weakness of the skeleton.

Pathological fractures present as a chalkstick fracture in long bones, and appear as a transverse fractures nearly 90 degrees to the long axis of the bone. In a pathological compression fracture of a spinal vertebra fractures will commonly appear to collapse the entire body of vertebra.

In circumstances where other pathologies are excluded (for example, cancer), a pathologic fracture is diagnostic of osteoporosis irrespective of bone mineral density.

In many cases there is pain and discomfort in a joint which increases over time. While it can affect any bone, about half of cases show multiple sites of damage. Avascular necrosis primarily affects the joints at the shoulder, knee, and hip. The classical sites are: head of femur, neck of talus and waist of the scaphoid.

Avascular necrosis most commonly affects the ends of long bones such as the femur (the bone extending from the knee joint to the hip joint). Other common sites include the humerus (the bone of the upper arm), knees, shoulders, ankles and the jaw.

Mild or early cases of Pagets are asymptomatic, and so most people are diagnosed with Paget's disease incidentally during medical evaluation for another problem. Approximately 35% of patients with Paget's have symptoms related to the disease when they are first diagnosed. Overall, the most common symptom is bone pain. When symptoms do occur, they may be confused with those of arthritis or other disorders, and so diagnosis may be delayed.

Paget's may first be noticed as an increasing deformity of a person's bones.

Paget's disease affecting the skull may lead to loss of hearing in one or both ears due to compression of the nerves in the inner ear. Rarely, skull involvement may lead to compression of the nerves that supply the eye, leading to vision loss.

Autosomal Dominant Osteopetrosis(ADO), also known as Albers-Schonberg disease. Most do not know they have this disorder because most individuals do not show any symptoms. However, the ones that do show symptoms, they will typically have a curvature of the spin(scoliosis), and multiple bone fractures. There are two types of adult osteopetrosis based on the basis of radiographic, biochemical, and clinical features.

Many patients will have bone pains. The defects are very common and include neuropathies due to the cranial nerve entrapment, osteoarthritis, carpal tunnel syndrome. About 40% of patients will experience recurrent fractures of their bones. 10% of patients will have osteomyelitis of the mandible.

Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on there may be no symptoms. Gradually joint pain may develop which may limit the ability to move. Complication may include collapse of the bone or nearby joint surface.

Risk factors include bone fractures, joint dislocations, alcoholism, and the use of high dose steroids. The condition may also occur without any clear reason. The most commonly affected bone is the femur. Other relatively common sites include the upper arm bone, knee, shoulder, and ankle. Diagnosis is typically by medical imaging such as X-ray, CT scan, or MRI. Rarely biopsy may be used.

Treatments may include medication, not walking on the affected leg, stretching, and surgery. Most of the time surgery is eventually required and may include core decompression, osteotomy, bone grafts, or joint replacement. About 15,000 cases occur per year in the United States. People 30 to 50 years old are most commonly affected. Males are more commonly affected than females.

Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws (the maxilla and the mandible). Various forms of ONJ have been described over the last 160 years, and a number of causes have been suggested in the literature.

Osteonecrosis of the jaw associated with bisphosphonate therapy, which is required by some cancer treatment regimens, has been identified and defined as a pathological entity (bisphosphonate-associated osteonecrosis of the jaw) since 2003. The possible risk from lower oral doses of bisphosphonates, taken by patients to prevent or treat osteoporosis, remains uncertain.

Treatment options have been explored; however, severe cases of ONJ still require surgical removal of the affected bone. A thorough history and assessment of pre-existing systemic problems and possible sites of dental infection are required to help prevent the condition, especially if bisphosphonate therapy is considered.

The major symptoms of OFC are bone pain or tenderness, bone fractures, and skeletal deformities such as bowing of the bones. The underlying hyperparathyroidism may cause kidney stones, nausea, constipation, fatigue and weakness. X-rays may indicate thin bones, fractures, bowing, and cysts. Fractures are most commonly localized in the arms, legs, or spine.

The addition of weight loss, appetite loss, vomiting, polyuria, and polydipsia to the aforementioned symptoms may indicate that OFC is the result of parathyroid carcinoma. Parathyroid carcinoma, an uncommon cancer of the parathyroid glands, is generally indicated by serum calcium levels higher than usual, even in comparison to the high serum calcium levels that OFC generally presents with. Symptoms are also often more severe. Generally, the presence of a palpable neck mass is also indicative of the cancer, occurring in approximately 50% of sufferers, but virtually nonexistent in individuals with OFC with a different origin.

The definitive symptom of ONJ is the exposure of mandibular or maxillary bone through lesions in the gingiva that do not heal. Pain, inflammation of the surrounding soft tissue, secondary infection or drainage may or may not be present. The development of lesions is most frequent after invasive dental procedures, such as extractions, and is also known to occur spontaneously. There may be no symptoms for weeks or months, until lesions with exposed bone appear. Lesions are more common on the mandible than the maxilla.

- Pain and neuropathy

- Erythema and suppuration

- Bad breath

Paget's disease of bone (commonly known as Paget's disease or historically, osteitis deformans) is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the microscopic level, specifically excessive bone breakdown and subsequent disorganized new bone formation. These structural changes cause the bone to weaken, which may result in deformity, pain, fracture, or arthritis of associated joints. The exact cause is unknown, although leading theories indicate both genetic and acquired factors ("see causes"). Paget's disease may affect any one or multiple bones of the body (most commonly pelvis, femur, and lumbar vertebrae, and skull), but never the entire skeleton, and does not spread from bone to bone. Rarely, a bone affected by Paget's disease can transform into a malignant bone cancer.

As the disease often affects people differently, treatments of Paget's disease can vary. Although there is no cure for Paget's disease, medications (bisphosphonates and calcitonin) can help control the disorder and lessen pain and other symptoms. Medications are often successful in controlling the disorder, especially when started before complications begin.

Paget's disease affects from 1.5 to 8.0 percent of the population, and is most common in those of British descent. It is primarily diagnosed in older people, and is rare in people less than 55 years of age. Men are more commonly affected than women (3:2).

The disease is named after Sir James Paget.

In osteochondritis dissecans, fragments of cartilage or bone become loose within a joint, leading to pain and inflammation. These fragments are sometimes referred to as joint mice. OCD is a type of osteochondrosis in which a lesion has formed within the cartilage layer itself, giving rise to secondary inflammation. OCD most commonly affects the knee, although it can affect other joints such as the ankle or the elbow.

People with OCD report activity-related pain that develops gradually. Individual complaints usually consist of mechanical symptoms including pain, swelling, catching, locking, popping noises, and buckling / giving way; the primary presenting symptom may be a restriction in the range of movement. Symptoms typically present within the initial weeks of stage I; however, the onset of stage II occurs within months and offers little time for diagnosis. The disease progresses rapidly beyond stage II, as OCD lesions quickly move from stable cysts or fissures to unstable fragments. Non-specific symptoms, caused by similar injuries such as sprains and strains, can delay a definitive diagnosis.

Physical examination typically reveals fluid in the joint, tenderness, and crepitus. The tenderness may initially spread, but often reverts to a well-defined focal point as the lesion progresses. Just as OCD shares symptoms with common maladies, acute osteochondral fracture has a similar presentation with tenderness in the affected joint, but is usually associated with a fatty hemarthrosis. Although there is no significant pathologic gait or characteristic alignment abnormality associated with OCD, the patient may walk with the involved leg externally rotated in an attempt to avoid tibial spine impingement on the lateral aspect of the medial condyle of the femur.

Osteitis fibrosa cystica is defined as the classic skeletal manifestation of advanced hyperparathyroidism. Under the ICD-10 classification system, established by the World Health Organization, OFC is listed under category E21.0, primary hyperparathyroidism.

The symptoms of Gorham's disease vary depending on the bones involved. It may affect any part of the skeleton, but the most common sites of disease are the shoulder, skull, pelvic girdle, jaw, ribs, and spine.

In some cases there are no symptoms until a fracture occurs either spontaneously or following minor trauma, such as a fall. There may be an acute onset of localized pain and swelling. More commonly there is pain of no apparent cause that increases in frequency and intensity over time and may eventually be accompanied by weakness and noticeable deformity of the area. The rate of progression is unpredictable and the prognosis can be difficult. The disease may stabilize after a number of years, go into spontaneous remission, or, in cases involving the chest and upper spine, prove fatal. Recurrence of the disease following remission can also occur. Involvement of the spine and skull base may cause a poor outcome from neurological complications. In many cases, the end result of Gorham's disease is severe deformity and functional disability.

Symptoms such as difficulty breathing and chest pain may be present if the disease is present in the ribs, scapula, or thoracic vertebrae. These may indicate that the disease has spread from the bone into the chest cavity. The breathing problems may be misdiagnosed as asthma, because the damage done to the lungs can cause the same types of changes to lung function testing that are seen in asthma. Extension of the lesions into the chest may lead to the development of chylous pleural and pericardial effusions. Chyle is rich in protein and white blood cells that are important in fighting infection. The loss of chyle into the chest can have serious consequences, including infection, malnutrition, and respiratory distress and failure. These complications or their symptoms, such as difficulty breathing, chest pain, poor growth or weight loss, and infection have sometimes been the first indications of the condition.

An endocrine bone disease is a bone disease associated with a disorder of the endocrine system. An example is osteitis fibrosa cystica.

Hematologic manifestations related to bone marrow suppression and subsequent pancytopenia are a major source of morbidity and mortality. Additionally extramedullary hematopoiesis can result in liver and spleen dysfunction. Cranial nerve dysfunction and neurologic complications are usually associated with infantile osteopetrosis. Expansion of the skull bone leads to macrocephaly. Additionally, linear growth retardation that is not apparent at birth, delayed motor milestones and poor dentition can occur.

The generalized increase in bone density of the medullary portion predominates with relative sparing of the cortices. The axial and appendicular skeleton are uniformly involved. Malignant infantile osteopetrosis is known for exhibiting specific plain radiographic abnormalities:

- Loss of differentiation between the medullary and cortical portions of bone is a radiographic hallmark of infantile osteopetrosis

- Characteristic endobone or “bone-within-bone” appearance in the spine, or “sandwich vertebra” appearance, characterized by dense endplate sclerosis with sharp margins

- Characteristic endobone or “bone-within-bone” appearance in the pelvis and long bones of extremities where areas of osteosclerosis intermingle with areas of relatively hypodense bone.

- Failure of remodeling of the distal femoral and proximal humeral metaphyses giving the affected bones a funnel shaped appearance known as (Erlenmeyer flask deformity)

- Alternating radiolucent femoral metaphyseal bands

- Pathologic fractures

PDP has a number of visible symptoms. Most important clinical features are: pachydermia (thickening and wrinkling of the skin), furrowing of the face and scalp, periostosis (swelling of periarticular tissue and shaggy periosteal new bone formation of long bones) and digital clubbing (enlargement of fingertips). Other features include excessive sweating, arthralgia and gastrointestinal abnormalities. An overview of all symptoms is provided in table 2.

Table 2. Overview of symptoms

For unknown reasons, children born with FOP have deformed big toes, possibly missing a joint or simply presenting with a notable lump at the minor joint. The first "flare-up" that leads to the formation of FOP bones usually occurs before the age of 10. The bone growth progresses from the top downward, just as bones grow in fetuses. A child with FOP will typically develop bones starting at the neck, then on the shoulders, arms, chest area and finally on the feet.

Specifically, ossification is typically first seen in the dorsal, axial, cranial and proximal regions of the body. Later the disease progresses in the ventral, appendicular, caudal and distal regions of the body. However, it does not necessarily occur in this order due to injury-caused flare-ups. Often, the tumor-like lumps that characterize the disease appear suddenly. This condition causes loss of mobility to affected joints, including inability to fully open the mouth limiting speech and eating. Extra bone formation around the rib cage restricts the expansion of lungs and diaphragm causing breathing complications.

Since the disease is so rare, the symptoms are often misdiagnosed as cancer or fibrosis. This leads physicians to order biopsies, which can exacerbate the growth of these lumps. However, those born with FOP tend to have malformed toes or thumbs which help distinguish this disorder from other skeletal problems.

The median age of survival is 40 years with proper management. However, delayed diagnosis, trauma and infections can decrease life expectancy.

Stress shielding refers to the reduction in bone density (osteopenia) as a result of removal of typical stress from the bone by an implant (for instance, the femoral component of a hip prosthesis). This is because by Wolff's law, bone in a healthy person or animal will remodel in response to the loads it is placed under. Therefore, if the loading on a bone decreases, the bone will become less dense and weaker because there is no stimulus for continued remodeling that is required to maintain bone mass.

To diagnose osteochondritis dissecans, an X-ray, CT scan or MRI scan can be performed to show necrosis of subchondral bone, formation of loose fragments, or both. Occasionally a nuclear medicine bone scan is used to assess the degree of loosening within the joint.

Renal osteodystrophy may exhibit no symptoms; if it does show symptoms, they include:

- Bone pain

- Joint pain

- Bone deformation

- Bone fracture

- The broader concept of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not only associated with fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). These clinical consequences are acquiring such an importance that scientific working groups (such as the ERA-EDTA CKD-MBD Working Group) or international initiatives are trying to promote research in the field including basic, translational and clinical research.

An osteolytic lesion (from the Greek words for "bone" (ὀστέον), and "to unbind" (λύειν)) is a softened section of a patient's bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma. This softened area appears as a hole on X-ray scans due to decreased bone density. Osteolytic lesions can cause pain, increased risk of bone fracture, and spinal chord compression. These lesions can be treated using biophosphonates or radiation, though new solutions are being tested in clinical trials.