The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Biophosphonates are drugs that are used to prevent bone mass loss and are often used to treat osteolytic lesions. Zoledronic acid (Reclast) is a specific drug given to cancer patients to prevent the worsening of bone lesions and has been reported to have anti-tumor effects as well. Zoledronic acid has been clinically tested in conjunction with calcium and vitamin D to encourage bone health. Denosumab, a monoclonal antibody treatment RANKl inhibitor that targets the osteocyte apoptosis regualtory RANKL gene, is also prescribed to prevent bone metastases and bone lesions. Most biophosphonates are co-prescribed with disease-specific treatments, such as chemotherapy or radiation for cancer patients.

The treatment should be tailored to the cause involved and the severity of the disease process. With oral osteoporosis the emphasis should be on good nutrient absorption and metabolic wastes elimination through a healthy gastro-intestinal function, effective hepatic metabolism of toxicants such as exogenous estrogens, endogenous acetaldehyde and heavy metals, a balanced diet, healthy lifestyle, assessment of factors related to potential coagulopathies, and treatment of periodontal diseases and other oral and dental infections.

In cases of advanced oral ischaemic osteoporosis and/or ONJ that are not bisphosphonates related, clinical evidence has shown that surgically removing the damaged marrow, usually by curettage and decortication, will eliminate the problem (and the pain) in 74% of patients with jaw involvement. Repeat surgeries, usually smaller procedures than the first, may be required. Almost a third of jawbone patients will need surgery in one or more other parts of the jaws because the disease so frequently present multiple lesions, i.e., multiple sites in the same or similar bones, with normal marrow in between. In the hip, at least half of all patients will get the disease in the opposite hip over time; this pattern occurs in the jaws as well. Recently, it has been found that some osteonecrosis patients respond to anticoagulation therapies alone. The earlier the diagnosis the better the prognosis. Research is ongoing on other non-surgical therapeutic modalities that could alone or in combination with surgery further improve the prognosis and reduce the morbidity of ONJ. A greater emphasis on minimizing or correcting known causes is necessary while further research is conducted on chronic ischaemic bone diseases such as oral osteoporosis and ONJ.

In patients with bisphosphonates-associated ONJ, the response to surgical treatment is usually poor. Conservative debridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses, and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this form of ONJ. Although an effective treatment for bisphosphonate-associated bone lesions has not yet been established, and this is unlikely to occur until this form of ONJ is better understood, there have been clinical reports of some improvement after 6 months or more of complete cessation of bisphosphonate therapy.

Treatment in fibrous dysplasia is mainly palliative, and is focused on managing fractures and preventing deformity. There are no medications capable of altering the disease course. Intravenous bisphosphonates may be helpful for treatment of bone pain, but there is no clear evidence that they strengthen bone lesions or prevent fractures. Surgical techniques that are effective in other disorders, such as bone grafting, curettage, and plates and screws, are frequently ineffective in fibrous dysplasia and should be avoided. Intramedullary rods are generally preferred for management of fractures and deformity in the lower extremities. Progressive scoliosis can generally be managed with standard instrumentation and fusion techniques. Surgical management in the craniofacial skeleton is complicated by frequent post-operative FD regrowth, and should focus on correction of functional deformities. Prophylactic optic nerve decompression increases the risk of vision loss and is contraindicated.

Managing endocrinopathies is a critical component of management in FD. All patients with fibrous dysplasia should be evaluated and treated for endocrine diseases associated with McCune–Albright syndrome. In particular untreated growth hormone excess may worsen craniofacial fibrous dysplasia and increase the risk of blindness. Untreated hypophosphatemia increases bone pain and risk of fractures.

The first three cases of bisphosphonate-associated osteonecrosis of the jaw were spontaneously reported to the FDA by an oral surgeon in 2002, with the toxicity being described as a potentially late toxicity of chemotherapy. In 2003 and 2004, three oral surgeons independently reported to the FDA information on 104 cancer patients with bisphosphonate-associated osteonecrosis of the jaw seen in their referral practices in California, Florida, and New York. These case series were published as peer-reviewed articles — two in the "Journal of Oral and Maxillofacial Surgery" and one in the "Journal of Clinical Oncology". Subsequently, numerous instances of persons with this ADR were reported to the manufacturers and to the FDA. By December 2006, 3607 cases of people with this ADR had been reported to the FDA and 2227 cases had been reported to the manufacturer of intravenous bisphosphonates.

The International Myeloma Foundation's web-based survey included 1203 respondents, 904 patients with myeloma and 299 with breast cancer and an estimate that after 36 months, osteonecrosis of the jaw had been diagnosed in 10% of 211 patients on zoledronate and 4% of 413 on pamidronate. A population based study in Germany identified more than 300 cases of osteonecrosis of the jaw, 97% occurring in cancer patients (on high-dose intravenous bisphosphonates) and 3 cases in 780,000 patients with osteoporosis for an incidence of 0.00038%. Time to event ranged from 23–39 months and 42–46 months with high dose intravenous and oral bisphosphonates. A prospective, population based study by Mavrokokki "et al.". estimated an incidence of osteonecrosis of the jaw of 1.15% for intravenous bisphosphonates and 0.04% for oral bisphosphonates. Most cases (73%) were precipitated by dental extractions. In contrast, safety studies sponsored by the manufacturer reported bisphosphonate-associated osteonecrosis of the jaw rates that were much lower.

Although the majority of cases of ONJ have occurred in cancer patients receiving high dose intravenous bisphosphonates, almost 800 cases have been reported in oral bisphosphonate users for osteoporosis or Pagets disease. In terms of severity most cases of ONJ in oral bisphosphonate users are stage 1–2 and tend to progress to resolution with conservative measures such as oral chlorhexidine rinses.

Owing to prolonged embedding of bisphosphonate drugs in the bone tissues, the risk for BRONJ is high even after stopping the administration of the medication for several years.

This form of therapy has been shown to prevent loss of bone mineral density (BMD) as a result of a reduction in bone turnover. However, bone health entails quite a bit more than just BMD. There are many other factors to consider.

In healthy bone tissue there is a homeostasis between bone resorption and bone apposition. Diseased or damaged bone is resorbed through the osteoclasts mediated process while osteoblasts form new bone to replace it, thus maintaining healthy bone density. This process is commonly called remodelling.

However, osteoporosis is essentially the result of a lack of new bone formation in combination with bone resorption in reactive hyperemia, related to various causes and contributing factors, and bisphosphonates do not address these factors at all.

In 2011, a proposal incorporating both the reduced bone turnover and the infectious elements of previous theories has been put forward. It cites the impaired functionality of affected macrophages as the dominant factor in the development of ONJ.

In a systematic review of cases of bisphosphonate-associated ONJ up to 2006, it was concluded that the mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. According to Woo, Hellstein and Kalmar, oversuppression of bone turnover is probably the primary mechanism for the development of this form of ONJ, although there may be contributing co-morbid factors (as discussed elsewhere in this article). It is recommended that all sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate (Fosamax), for osteoporosis is uncertain and warrants careful monitoring. Patients taking dexamethasone and other glucocorticoids are at increased risk.

Matrix metalloproteinase 2 may be a candidate gene for bisphosphonate-associated osteonecrosis of the jaw, since it is the only gene known to be associated with bone abnormalities and atrial fibrillation, both of which are side effects of bisphosphonates.

Bone lesions in multiple myeloma patients may be treated with low-dose radiation therapy in order to reduce pain and other symptoms. Used in combination with immunochemotherapy, radiation therapy can be used to treat certain cancers when aimed at areas of bone lesion and softened bone.

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

A variety of methods may be used to treat the most common being the total hip replacement (THR). However, THRs have a number of downsides including long recovery times and short life spans (of the hip joints). THRs are an effective means of treatment in the older population; however, in younger people they may wear out before the end of a person's life.

Other technicques such as metal on metal resurfacing may not be suitable in all cases of avascular necrosis; its suitability depends on how much damage has occurred to the femoral head. Bisphosphonates which reduces the rate of bone breakdown may prevent collapse (specifically of the hip) due to AVN.

The effective treatment for PDP is currently unknown due to the lack of controlled data and is largely based on case reports. Although the HPGD enzyme is likely to be involved into the pathogenesis of PDP, no strategies against this mutation have been reported yet, since it is hard to tackle a defective enzyme. Gene therapy could be a solution for this, although this has not been reported yet in literature.

Conventional PDP drug treatment to decrease inflammation and pain includes NSAIDs and corticosteroids. Other drugs used by PDP patients target bone formation or skin manifestations. Surgical care is used to improve cosmetic appearance.

The amount of disability that results from avascular necrosis depends on what part of the bone is affected, how large an area is involved, and how effectively the bone rebuilds itself. The process of bone rebuilding takes place after an injury as well as during normal growth. Normally, bone continuously breaks down and rebuilds—old bone is resorbed and replaced with new bone. The process keeps the skeleton strong and helps it to maintain a balance of minerals. In the course of avascular necrosis, however, the healing process is usually ineffective and the bone tissues break down faster than the body can repair them. If left untreated, the disease progresses, the bone collapses, and the joint surface breaks down, leading to pain and arthritis.

Five bisphosphonates are currently available. In general, the most commonly prescribed are risedronic acid, alendronic acid, and pamidronic acid. Etidronic acid and other bisphosphonates may be appropriate therapies for selected patients but are less commonly used. None of these drugs should be used by people with severe kidney disease.

- Etidronate disodium The approved regimen is once daily for six months; a higher dose is more commonly used. No food, beverage, or medications should be consumed for two hours before and after taking. The course should not exceed six months, but repeat courses can be given after rest periods, preferably of three to six months duration.

- Pamidronate disodium in intravenous form: the approved regimen uses an infusion over four hours on each of three consecutive days, but a more commonly used regimen is over two to four hours for two or more consecutive or nonconsecutive days.

- Alendronate sodium is given as tablets once daily for six months; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).

- Tiludronate disodium are taken once daily for three months; they may be taken any time of day, as long as there is a period of two hours before and after resuming food, beverages, and medications.

- Risedronate sodium tablet taken once daily for 2 months is the prescribed regimen; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).

- Zoledronic acid is given as an intravenous infusion; a single dose is effective for two years. This is recommended for most people at high risk with active disease.

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

The only effective line of treatment for malignant infantile osteopetrosis is hematopoietic stem cell transplantation. It has been shown to provide long-term disease-free periods for a significant percentage of those treated; can impact both hematologic and skeletal abnormalities; and has been used successfully to reverse the associated skeletal abnormalities.

Radiographs of at least one case with malignant infantile osteopetrosis have demonstrated bone remodeling and recanalization of medullar canals following hematopoietic stem cell transplantation. This favorable radiographic response could be expected within one year following the procedure - nevertheless, primary graft failure can prove fatal.

Calcitonin, also called calcitonin-salmon, is a synthetic copy of a polypeptide hormone secreted by the ultimobranchial gland of salmon. Miacalcin is administered by injection, three times per week or daily, for 6–18 months. Repeat courses can be given after brief rest periods. Miacalcin may be appropriate for certain patients, but is seldom used. Calcitonin is also linked to increased chance of cancer. Due to the increased risk of cancer, the European Medicines Agency (EMA) recommended that calcitonin be used only on a short-term basis for 3 conditions for which it had previously been approved in the European Union: Paget's disease, acute bone loss resulting from sudden immobilization, and hypercalcemia caused by cancer.

The EMA said it based its recommendations on a review of the benefits and risks of calcitonin-containing medicines. Conducted by the agency's Committee for Medicinal Products for Human Use (CHMP), the review encompassed available data from the companies that market these drugs, postmarketing safety data, randomized controlled studies, 2 studies of unlicensed oral calcitonin drugs, and experimental cancer studies, among other sources.

CHMP found that "a higher proportion of patients treated with calcitonin for long periods of time develop cancer of various types, compared with patients taking placebo." The increase in cancer rates ranged from 0.7% for oral formulations to 2.4% for the nasal formulation. CHMP concluded that the benefits of calcitonin for osteoporosis did not exceed the risks. The nasal spray's only indication is for osteoporosis, thus justifying the drug's removal from the market.

As a solution for injection or infusion, calcitonin should be administered for no more than 4 weeks to prevent acute bone loss resulting from sudden immobilization, and normally for no more than 3 months to treat Paget's disease, the EMA said. The agency did not specify a time frame for the short-term use of calcitonin for treating hypercalcemia caused by cancer.

There is no cure, although curative therapy with bone marrow transplantion is being investigated in clinical trials. It is believed the healthy marrow will provide the sufferer with cells from which osteoclasts will develop. If complications occur in children, patients can be treated with vitamin D. Gamma interferon has also been shown to be effective, and it can be associated to vitamin D. Erythropoetin has been used to treat any associated anemia. Corticosteroids may alleviate both the anemia and stimulate bone resorption. Fractures and osteomyelitis can be treated as usual. Treatment for osteopetrosis depends on the specific symptoms present and the severity in each person. Therefore, treatment options must be evaluated on an individual basis. Nutritional support is important to improve growth and it also enhances responsiveness to other treatment options. A calcium-deficient diet has been beneficial for some affected people.

Treatment is necessary for the infantile form:

- Vitamin D (calcitriol) appears to stimulate dormant osteoclasts, which stimulates bone resorption

- Gamma interferon can have long-term benefits. It improves white blood cell function (leading to fewer infections), decreases bone volume, and increases bone marrow volume.

- Erythropoietin can be used for anemia, and corticosteroids can be used for anemia and to stimulate bone resorption.

Bone marrow transplantation (BMT) improves some cases of severe, infantile osteopetrosis associated with bone marrow failure, and offers the best chance of longer-term survival for individuals with this type.

In pediatric (childhood) osteopetrosis, surgery is sometimes needed because of fractures. Adult osteopetrosis typically does not require treatment, but complications of the condition may require intervention. Surgery may be needed for aesthetic or functional reasons (such as multiple fractures, deformity, and loss of function), or for severe degenerative joint disease.

The long-term-outlook for people with osteopetrosis depends on the subtype and the severity of the condition in each person.The severe infantile forms of osteopetrosis are associated with shortened life expectancy, with most untreated children not surviving past their first decade. seems to have cured some infants with early-onset disease. However, the long-term prognosis after transplantation is unknown. For those with onset in childhood or adolescence, the effect of the condition depends on the specific symptoms (including how fragile the bones are and how much pain is present). Life expectancy in the adult-onset forms is normal.

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.

Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are most used in PDP treatment. These drugs inhibit cyclo-oxygenase activity and thereby prostaglandin synthesis. Since PGE is likely to be involved in periosteal bone formation and acroosteolysis, this is why these drugs can alleviate the polyarthritis associated with PDP. In addition, NSAIDs and corticosteroids decrease formation of inflammatory mediators, reducing inflammation and pain. In case of possible gastropathy, the COX-2 selective NSAID etorixocib is preferred.

Infliximab can reduce pain and arthritis in PDP. It is a monoclonal antibody that blocks the biological action of TNF-α (tumor necrosis factor-alpha). TNF-α is an inflammatory cytokine found in high levels in PDP and it is involved in the production of other inflammatory mediators which increase the expression of RANKL. RANKL is thought to increase bone resorption.

Certain medications have been associated with an increase in osteoporosis risk; only glucocorticosteroids and anticonvulsants are classically associated, but evidence is emerging with regard to other drugs.

- Steroid-induced osteoporosis (SIOP) arises due to use of glucocorticoids – analogous to Cushing's syndrome and involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug prednisone is a main candidate after prolonged intake. Some professional guidelines recommend prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months. Alternate day use may not prevent this complication.

- Barbiturates, phenytoin and some other enzyme-inducing antiepileptics – these probably accelerate the metabolism of vitamin D.

- L-Thyroxine over-replacement may contribute to osteoporosis, in a similar fashion as thyrotoxicosis does. This can be relevant in subclinical hypothyroidism.

- Several drugs induce hypogonadism, for example aromatase inhibitors used in breast cancer, methotrexate and other antimetabolite drugs, depot progesterone and gonadotropin-releasing hormone agonists.

- Anticoagulants – long-term use of heparin is associated with a decrease in bone density, and warfarin (and related coumarins) have been linked with an increased risk in osteoporotic fracture in long-term use.

- Proton pump inhibitors – these drugs inhibit the production of stomach acid; this is thought to interfere with calcium absorption. Chronic phosphate binding may also occur with aluminium-containing antacids.

- Thiazolidinediones (used for diabetes) – rosiglitazone and possibly pioglitazone, inhibitors of PPARγ, have been linked with an increased risk of osteoporosis and fracture.

- Chronic lithium therapy has been associated with osteoporosis.

Recovery from renal osteodystrophy has been observed following kidney transplantation. Renal osteodystrophy is a chronic condition with a conventional hemodialysis schedule. Nevertheless, it is important to consider that the broader concept of CKD-MBD, which includes renal osteodystrophy, is not only associated with bone disease and increased risk of fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). Actually, bone may now be considered a new endocrine organ at the heart of CKD-MBD.

Treatment options include modified activity with or without weight bearing; immobilization; cryotherapy; anti-inflammatory medication; drilling of subchondral bone; microfracture; removal or reattachment of loose bodies; mosaicplasty and osteoarticular transfer system (OATS) procedures. The primary goals of treatment are:

1. Enhance the healing potential of subchondral bone;

2. Fix unstable fragments while maintaining joint congruity; and

3. Replace damaged bone and cartilage with implanted tissues or cells that can grow cartilage.

The articular cartilage's capacity for repair is limited: partial-thickness defects in the articular cartilage do not heal spontaneously, and injuries of the articular cartilage which fail to penetrate subchondral bone tend to lead to deterioration of the articular surface. As a result, surgery is often required in even moderate cases where the osteochondral fragment has not detached from the bone (Anderson Stage II, III).

The choice of surgical versus non-surgical treatments for osteochondritis dissecans is controversial. Consequently, the type and extent of surgery necessary varies based on patient age, severity of the lesion, and personal bias of the treating surgeon—entailing an exhaustive list of suggested treatments. A variety of surgical options exist for the treatment of persistently symptomatic, intact, partially detached, and completely detached OCD lesions. Post-surgery reparative cartilage is inferior to healthy hyaline cartilage in glycosaminoglycan concentration, histological, and immunohistochemical appearance. As a result, surgery is often avoided if non-operative treatment is viable.

Studies of the benefits of supplementation with calcium and vitamin D are conflicting, possibly because most studies did not have people with low dietary intakes. A 2013 review by the USPSTF found insufficient evidence to determine if supplementation with calcium and vitamin D results in greater harm or benefit in men and premenopausal women. The USPSTF did not recommend low dose supplementation (less than 1 g of calcium and 400 IU of vitamin D) in postmenopausal women as there does not appear to be a difference in fracture risk. It is unknown what effect higher doses have. A 2015 review found little data that supplementation of calcium decreases the risk of fractures.

While some meta-analyses have found a benefit of vitamin D supplements combined with calcium for fractures, they did not find a benefit of vitamin D supplements alone.

While supplementation does not appear to affect the risk of death, there is an increased risk of myocardial infarctions with calcium supplementation, kidney stones, and stomach problems.

Vitamin K deficiency is also a risk factor for osteoporotic fractures. The gene gamma-glutamyl carboxylase (GGCX) is dependent on vitamin K. Functional polymorphisms in the gene could attribute to variation in bone metabolism and BMD. Vitamin K2 is also used as a means of treatment for osteoporosis and the polymorphisms of GGCX could explain the individual variation in the response to treatment of vitamin K. Vitamin K supplementation may reduce the risk of fractures in postmenopausal women; however, there is no evidence for men.

Medical management of OFC consists of Vitamin D treatment, generally alfacalcidol or calcitriol, delivered intravenously. Studies have shown that in cases of OFC caused by either end-stage renal disease or primary hyperparathyoidism, this method is successful not only in treating underlying hyperparathyoidism, but also in causing the regression of brown tumors and other symptoms of OFC.

Treatment for renal osteodystrophy includes the following:

- calcium and/or native vitamin D supplementation

- restriction of dietary phosphate (especially inorganic phosphate contained in additives)

- phosphate binders such as calcium carbonate, calcium acetate, sevelamer hydrochloride or carbonate, lanthanum carbonate, sucroferric oxyhydroxide, ferric citrate among others

- active forms of vitamin D (calcitriol, alfacalcidol, paricalcitol, maxacalcitol, doxercalciferol, among others)

- cinacalcet

- renal transplantation

- haemodialysis five times a week is thought to be of benefit

- parathyroidectomy for symptomatic medication refractive end stage disease

Clinical trials of isotretinoin, etidronate with oral corticosteroids, and perhexiline maleate have failed to demonstrate effectiveness, though the variable course of the disease and small prevalence induces uncertainty.

A handful of pharmaceutical companies focused on rare disease are currently in varying stages of investigation into different therapeutic approaches for FOP.

In August 2015, U.S. Food and Drug Administration (FDA) Office of Orphan Products Development granted La Jolla Pharmaceuticals orphan drug designation for two novel compounds for FOP. The compounds are small-molecule kinase inhibitors designed to selectively block ACVR1 (ALK2).

In August 2015, Clementia Pharmaceuticals also began the enrollment of children (ages 6 and above) into its Phase II clinical trial investigating palovarotene for the treatment of FOP. Preclinical studies demonstrated that palovarotene, a retinoic acid receptor gamma agonist, blocked abnormal bone formation in animal models via inhibition of secondary messenger systems in the BMP pathway. Clementia licensed palovarotene from Roche Pharmaceuticals, which previously evaluated the compound in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease. Palovarotene received Fast Track designation from the U.S. Food and Drug Administration (FDA) and orphan designations for the treatment of FOP from both the FDA and the European Medicines Agency (EMA).

In September 2015, Regeneron announced new insight into the mechanism of disease involving the activation of the ACVR1 receptor by activin A. In 2016, the company initiated a phase 1 study of its activin antibody, REGN 2477, in healthy volunteers; a phase 2 trial in FOP patients is planned for 2017.

Another potential therapeutic approach involves allele-specific RNA interference that targets mutated mRNA for degradation while preserving normal ACVR1 gene expression.

Further investigation into the mechanisms of heterotopic bone formation in FOP could aid in the development of treatments for other disorders involving extra-skeletal bone formation.