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.

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.

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

"Cleidocranial dysostosis" is a general skeletal condition named for the collarbone (cleido-) and cranium deformities which people with it often have. Common features include:

- Partly or completely missing collarbones.

- A soft spot or larger soft area in the top of the head where the fontanelle failed to close.

- Bones and joints are underdeveloped.

- The permanent teeth include supernumerary teeth.

- Permanent teeth not erupting

- Bossing (bulging) of the forehead.

- Hypertelorism

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.

In the animal kingdom there also exists a non-pathological form of osteosclerosis, resulting in unusually solid bone structure with little to no marrow. It is often seen in aquatic vertebrates, especially those living in shallow waters, providing ballast as an adaptation for an aquatic lifestyle. It makes bones heavier, but also more fragile. In those animal groups osteosclerosis often occurs together with bone thickening (pachyostosis). This joint occurrence is called pachyosteosclerosis.

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.

"Fibrous dysplasia" causes bone thinning and growths or lesions in one or more bones of the human body.

These lesions are tumor-like growths that consist of replacement of the medullary bone with fibrous tissue, causing the expansion and weakening of the areas of bone involved. Especially when involving the skull or facial bones, the lesions can cause externally visible deformities. The skull is often, but not necessarily, affected, and any other bone(s) can be involved.

Osteopenia is a condition in which bone mineral density is lower than normal. It is considered by many doctors to be a precursor to osteoporosis. However, not every person diagnosed with osteopenia will develop osteoporosis. More specifically, osteopenia is defined as a bone mineral density T-score between −1.0 and −2.5.

Osteosclerosis is a disorder that is characterized by abnormal hardening of bone and an elevation in bone density. It may predominantly affect the medullary portion and/or cortex of bone. Plain radiographs are a valuable tool for detecting and classifying osteosclerotic disorders. It can manifest in localized or generalized osteosclerosis. Localized osteosclerosis can be caused by Legg–Calvé–Perthes disease, sickle-cell disease and osteoarthritis among others. Osteosclerosis can be classified in accordance with the causative factor into acquired and hereditary.

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.

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

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.

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.

Pathologic fractures in children and adolescents can result from a diverse array of disorders namely; metabolic, endocrine, neoplastic, infectious, immunologic, and genetic skeletal dysplasias.

- Osteogenesis imperfecta

- Primary hyperparathyroidism

- Simple bone cyst

- Aneurismal bone cyst

- Disuse osteoporosis

- Chronic osteomyelitis

- Osteogenesis imperfecta

- Rickets

- Renal osteodystrophy

- Malignant infantile osteopetrosis

- juvenile osteoporosis

- juvenile rheumatoid arthritis

Like osteoporosis, osteopenia occurs more frequently in post-menopausal women as a result of the loss of estrogen. It can also be exacerbated by lifestyle factors such as lack of exercise, excess consumption of alcohol, smoking or prolonged use of glucocorticoid medications. It can also be a result of exposure to radiation.

Osteopenia occurs more frequently in participants in non-weight-bearing sports like bicycling or swimming than in participants in weight-bearing sports like powerlifting and running, since bone-loading exercise tends to protect or possibly increase bone mineral density.

In particular, the condition is often noted in young female athletes. It is one of the three major components of female athlete triad syndrome, along with amenorrhea and disordered eating. Female athletes tend to have lower body weight, lower fat percentage, and higher incidence of asthma than their less active peers. A chronic negative energy balance can suppress estrogen levels and decrease bone mineral density.

It is also a sign of normal aging, in contrast to osteoporosis which is present in pathologic aging.

Osteopenia is also a common effect of coeliac disease, even among patients who are otherwise asymptomatic.

Monostotic fibrous dysplasia (or monostotic osteitis fibrosa) is a form of fibrous dysplasia where only one bone is involved. It comprises a majority of the cases of fibrous dysplasia.

A rare bone disorder characterized by benign bone growths which can cause very painful swellings and bone deformities and makes bone prone to fractures.

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.

Fibrochondrogenesis is a congenital disorder presenting several features and radiological findings, some which distinguish it from other osteochondrodysplasias. These include: fibroblastic dysplasia and fibrosis of chondrocytes (cells which form cartilage); and flared, widened

long bone metaphyses (the portion of bone that grows during childhood).

Other prominent features include dwarfism, shortened ribs that have a appearance, micrognathism (severely underdeveloped jaw), macrocephaly (enlarged head), thoracic hypoplasia (underdeveloped chest), enlarged stomach, platyspondyly (flattened spine), and the somewhat uncommon deformity of tongue (in which the tongue appears split, resembling that of a reptile).

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.

The afflicted may have relatively small amounts of pain that will quickly increase in severity over a time period of 6–12 weeks. The skin temperature around the bone may increase, a bony swelling may be evident, and movement may be restricted in adjacent joints.

Spinal lesions may cause quadriplegia and patients with skull lesions may have headaches.

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

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.

Melorheostosis is a mesenchymal dysplasia manifesting as regions of dripping wax appearance or flowing candle wax appearance. It is thought to be caused by a mutation of the LEMD3 gene. The disorder can be detected by radiograph due to thickening of bony cortex resembling "dripping candle wax". It is included on the spectrum of developmental bone dysplasias including pycnodysostosis and osteopoikilosis. The disorder tends to be unilateral and monostotic (i.e. affecting a single bone), with only one limb typically involved. Cases with involvement of multiple limbs, ribs, and bones in the spine have also been reported. There are no reported cases of involvement of skull or facial bones. Melorheostosis can be associated with pain, physical deformity, skin and circulation problems, contractures, and functional limitation. It is also associated with a benign inner ear dysplasia known as osteosclerosis.

It is not known if LEMD3 mutations can cause isolated melorheostosis in the absence of Buschke-Ollendorff syndrome.