Osteopetrosis Treatment & Management
- Author: Robert Blank, MD, PhD; Chief Editor: George T Griffing, MD more...
Approach Considerations
Infantile osteopetrosis
Infantile osteopetrosis warrants treatment because of the adverse outcome associated with the disease.[15] Vitamin D (calcitriol) appears to help by stimulating dormant osteoclasts, thus stimulating bone resorption. Large doses of calcitriol, along with restricted calcium intake, sometimes improve osteopetrosis dramatically.[16] However, calcitriol 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 white blood cell function, greatly decreasing the incidence of new infections. With treatment, trabecular bone volume substantially decreases and bone-marrow volume increases. This results in 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 also been used to treat anemia, as well as to stimulate bone resorption. In one study, corticosteroids resulted in a striking increase in red blood cell 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/day is usually administered for months to years. Steroids are not the preferred treatment option.
Adult osteopetrosis
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 treatment
In pediatric osteopetrosis, surgical treatment is sometimes necessary because of fractures. The constellation of problems associated with this condition and the prevailing opinions regarding their management have been reviewed.[17]
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.
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 patient growth. It also enhances responsiveness to other treatment options. A calcium-deficient diet has shown some success in patients. However, patients may need calcium if hypocalcemia or rickets becomes a problem.
Bone Marrow Transplantation
BMT markedly improves some cases of infantile osteopetrosis.[18] BMT can cure 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. Magnetic resonance imaging (MRI) can be used to assess bones over time after BMT.
Hypercalcemia in bone marrow transplantation
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.[19] The hypercalcemia resolved following treatment with isotonic saline, furosemide, and subcutaneous calcitonin.
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Cleiren E, Benichou O, Van Hul E, et al. Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet. Dec 1 2001;10(25):2861-7. [Medline].
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| Characteristic | Adult onset | Infantile | Intermediate |
| Inheritance | Autosomal dominant | Autosomal recessive | Autosomal recessive |
| Bone marrow failure | None | Severe | None |
| Prognosis | Good | Poor | Poor |
| Diagnosis | Often diagnosed incidentally | Usually diagnosed before age 1y | Not applicable |
| Gene | Protein | Lesion | Phenotype | Human Equivalent | Key References |
| Csf1 | M-CSF | Naturally occurring op allele (frame shift) | Reduced size, short limbs, domed skull, absence of teeth, poor hearing, poor fertility, extramedullary hematopoiesis, rescued by administration of M-CSF | None known | Yoshida et al, 1990 |
| Csf1r | M-CSF receptor | Targeted disruption in exon 3 | Reduced size, short limbs, domed skull, absence of teeth, poor fertility, extramedullary hematopoiesis, slightly more severe than Csf1opphenotype | None known | Dai et al, 2002 |
| Tnfsf11 | RANKL | Targeted disruptions | Osteopetrosis, failure of lymph nodes to develop | None known | Kong et al, 1999; Kim et al, 2000 |
| Tnfrsf11a | RANK | Targeted disruptions | Osteopetrosis, failure of lymph nodes to develop | Duplications in exon 1 found in Paget disease and in familial expansile osteolysis | Li et al, 2000 |
| Ostm1 | Osteopetrosis-associated transmembrane protein 1 | Naturally occurring deletion | Abnormal coat color, short lifespan, chondrodysplasia, failure of tooth eruption, osteopetrosis | Infantile malignant osteopetrosis | Chalhoub et al, 2003 |
| Acp5 | Tartrate resistant acid phosphatase (acid phosphatase 5) | Targeted disruption | Chondrodysplasia, osteopetrosis | None known | Hayman et al, 1996 |
| Car2 | Carbonic anhydrase II | N -ethyl-N -nitrosourea (ENU) mutagenesis | No skeletal phenotype in mouse, renal tubular acidosis, growth retardation | Osteopetrosis with renal tubular acidosis | Lewis et al, 1988 |
| Clcn7 | Chloride channel 7 | Targeted disruptions | Chondrodysplasia, osteopetrosis, failure of tooth eruption, optic atrophy, retinal degeneration, premature death | Autosomal dominant type 2 osteopetrosis, autosomal recessive osteopetrosis | Kornak et al, 2001; Cleiren et al, 2001 |
| Ctsk | Cathepsin K | Targeted disruption | Osteopetrosis with increased osteoclast surface | Pycnodysostosis | Saftig et al, 1998; Kiviranta et al, 2005 |
| Gab2 | Grb2 -associated binder 2 | Targeted disruption | Osteopetrosis, defective osteoclast maturation | None known | Wada et al, 2005 |
| Mitf | Micro-ophthalmia–associated transcription factor | Spontaneous mutations, ENU mutagenesis, radiation mutagenesis, targeted disruption, untargeted insertional mutagenesis | Pigmentation failure, failure of tooth eruption, osteopetrosis, microphthalmia, infertility in both sexes | Waardenburg syndrome, type 2a; Tietz syndrome, ocular albinism with sensorineural deafness | Hodgkinson et al, 1993; Steingrimsson et al, 1994 |
| Src | c-SRC | Targeted disruption | Osteopetrosis, failure of tooth eruption, premature death, reduced body size, female infertility, poor nursing | None known | Soriano et al, 1991 |
| Tcirg1 | 116-kD subunit of vacuolar proton pump | Spontaneous deletion, targeted disruption | Osteopetrosis, failure of tooth eruption, chondrodysplasia, small size, premature death | Autosomal recessive osteopetrosis | Li et al, 1999; Scimeca et al, 2000; Frattini et al, 2000 |
| Traf6 | Tumor necrosis factor (TNF)-receptor–associated factor 6 | Targeted disruptions | Osteopetrosis, failure of tooth eruption, decreased body size, premature death, impaired maturation of dendritic cells | None known | Naito et al, 1999; Lomaga et al, 1999; Kobayashi et al, 2003 |
| Characteristic | Type I | Type II |
| Skull sclerosis | Marked sclerosis mainly of the vault | Sclerosis mainly of the base |
| Spine | Does not show much sclerosis | Shows the rugger-jersey appearance |
| Pelvis | No endobones | Shows endobones in the pelvis |
| Transverse banding of metaphysis | Absent | May or may not be present |
| Risk of fracture | Low | High |
| Serum acid phosphatase | Normal | Very high |
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