eMedicine Specialties > Endocrinology > Metabolic Bone Disease
Osteopetrosis: Treatment & Medication
Updated: Oct 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Infantile osteopetrosis warrants treatment because of the adverse outcome associated with the disease.13
- Vitamin D (calcitriol) appears to help by stimulating dormant osteoclasts and thus stimulating bone resorption. Large doses of calcitriol, along with restricted calcium intake, sometimes improve osteopetrosis dramatically.14 It usually produces only modest clinical improvement, which is not sustained after therapy is discontinued.
- Treatment with gamma interferon has produced long-term benefits. It improves WBC function, greatly decreasing the incidence of new infections. With treatment, trabecular bone volume substantially decreases, and bone-marrow volume increases. This effect increases in hemoglobin, platelet counts, and survival rates. Combination therapy with calcitriol is clearly superior to calcitriol alone.
- Erythropoietin can be used to correct anemia.
- Corticosteroids have been used to stimulate bone resorption and treat anemia. In one study, corticosteroids resulted in a striking increase in RBC mass and platelet count, but failed to improve bone mass. This effect on blood cells is due to reduced destruction in the reticuloendothelial system. Prednisone 1-2 mg/kg/d is usually administered for months to years. Steroids are not the preferred treatment option.
- Adult osteopetrosis requires no treatment by itself, although complications of the disease may require intervention. No specific medical treatment exists for the adult type.
Surgical Care
- BMT markedly improves some cases of infantile osteopetrosis.15
- BMT can cure both bone marrow failure and metabolic abnormalities in patients whose disease arises from an intrinsic defect of the osteoclast lineage.
- BMT is the only curative treatment for this disease. However, BMT may be limited to a subset of patients whose defects are extrinsic to the osteoclast lineage and whose condition is unlikely to respond. Moreover, this approach is limited because an appropriate bone marrow donor is not always found. Also, BMT poses considerable risk because of the necessity for profound immunosuppression and the possibility of a graft-versus-host reaction.
- In pediatric osteopetrosis, surgical treatment is sometimes necessary because of fractures. This constellation of problems and prevailing opinions regarding management has been reviewed.16
- In adult osteopetrosis, surgical treatment may be needed for aesthetic reasons (eg, in patients with notable facial deformity) or for functional reasons (eg, in patients with multiple fractures, deformity, and loss of function). Severe, related degenerative joint disease may warrant surgical intervention as well.
- Hypercalcemia can occur following hematopoietic cell transplantation (HCT), owing to the engraftment of osteoclasts arising from precursor cells. In a study of 15 patients with osteopetrosis, Martinez et al found that posttransplantation hypercalcemia developed in 40% of these individuals, occurring primarily in patients over age 2 years at the time of the HCT; the median time to onset was 23 days.17 The hypercalcemia resolved following treatment with isotonic saline, furosemide, and subcutaneous calcitonin.
Consultations
Refer patients to an endocrinologist with special interest and experience in bone and mineral metabolism. A patient-oriented Web site provides the names of several experts in the field.
Diet
Nutritional support is important to improve growth of patients. It also enhances responsiveness to other treatment options. Calcium deficient diet has shown some success in these patients. On the contrary, patients might need calcium if hypocalcemia or rickets becomes a problem.
Activity
Counsel patients to avoid activities that might increase their risk of fractures.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Some of the medications include vitamin-D supplements, corticosteroids, interferon, and erythropoietin.
Vitamin-D supplements
These supplements increase serum calcium levels by increasing calcium absorption from the GI tract.
Calcitriol (Rocaltrol, Calcijex)
In large doses, with restricted calcium intake, sometimes improves osteopetrosis dramatically. Can be used to treat infantile osteopetrosis and appears to help by stimulating dormant osteoclasts and thus bone resorption. Markers of bone turnover (eg, serum osteocalcin, bone-specific alkaline phosphatase, urine hydroxyproline levels) increase during therapy. Usually produces only modest clinical improvement, which is not sustained after discontinuation.
Adult
Pediatric
15 ng/kg/d PO initially, followed by maintenance dose of 5-40 ng/kg/d PO
Cholestyramine and colestipol decrease absorption; magnesium-containing antacids and thiazide diuretics can increase effects
Documented hypersensitivity; hypercalcemia; hypercalciuria
Pregnancy
Precautions
May need to restrict calcium intake to prevent hypercalcemia; maintain adequate fluid intake
Interferons
These agents delay disease progression in severe, malignant osteopetrosis.18 Combined with calcitriol, interferons are substantially more effective than calcitriol alone. The combination reduces incidence of severe infections, the number of transfusions needed, and the patient’s bone mass considerably more than calcitriol alone. The US Food and Drug administration approved in 2000 for use in children with osteopetrosis.
Interferon gamma 1b (Actimmune)
Interferons synthesized by eukaryotic cells in response to viruses and variety of natural and synthetic stimuli. Possesses antiviral, immunomodulatory, and antiproliferative activity. Interferon gamma has potent phagocyte-activating effects not seen with other interferon preparations. Works by stimulating osteoclast activity.
Adult
Pediatric
<1 year: Not established
>1 year:
Body surface area <0.5 m2: 1.5 mcg/kg/dose SC 3 times/wk (eg, Monday, Wednesday, Friday)
Body surface area >0.5 m2: 50 mcg (1 million IU)/ m2/dose SC 3 times/wk (eg, Monday, Wednesday, Friday)
May inhibit cytochrome P450 (CYP450) isoenzymes; coadministration with other myelosuppressive agents (eg, antineoplastic agents) may increase risk of neutropenia, anemia, or thrombocytopenia
Documented hypersensitivity, including that related to Escherichia coli
Pregnancy
Precautions
May cause CNS toxicity (eg, decreased mental status, gait disturbance, dizziness), myelosuppression, or exacerbate existing cardiovascular disease; impairs fertility
More on Osteopetrosis |
| Overview: Osteopetrosis |
| Differential Diagnoses & Workup: Osteopetrosis |
 Treatment & Medication: Osteopetrosis |
| Follow-up: Osteopetrosis |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Further Reading
Clinical guidelines:
Evaluating infants and young children with multiple fractures. American Academy of Pediatrics - Medical Specialty Society. 2006 Sep. 5 pages. NGC:005253
Clinical trials:
Allogeneic Transplantation For Severe Osteopetrosis
rhPTH Therapy for Low Turnover Bone Fragility
Keywords
osteopetrosis, osteoclast, osteoblast osteoclast, osteosclerosis, osteosclerotic, Albers-Schönberg disease, marble bone disease, osteoclastic bone resorption, infantile osteopetrosis, infantile malignant osteopetrosis, adult osteopetrosis, benign osteopetrosis
