Hypophosphatemic rickets/osteomalacia is a rare disorder characterized by renal phosphate wasting and inappropriately low levels of calcitriol causing hypophosphatemia and abnormal bone mineralization.  Medical treatment of the diseases includes activated vitamin D analogs, however, the administration dose is often limited because of side effects such as hypercalcemia and/or hypercalciuria.

To assess the efficacy of cinacalcet for treatment of hypophosphatemic rickets/osteomalacia, it was administered to four patients (2 X-linked hypophosphatemic rickets, 1 adefovir-induced hypophosphatemic osteomalacia, and 1 oncogenic osteomalacia) who were already being treated with alfacalcidol, an active vitamin D analog.  The doses of alfacalcidol were adjusted so that the patients would not exhibit hypercalcemia and hypercalciuria before cinacalcet administration.  These doses were then fixed for the first year, but could be adjusted in the second year.

The addition of cinacalcet 25 mg/day reduced patient serum PTH and calcium levels by 46% and 9%, respectively, in the first year.  The reduced serum PTH resulted in increased phosphate reabsorption, as shown by the increment of maximum tubular reabsorption rate to glomerular filtration rate by 112%.  As a result, serum phosphate levels increased by 38%, which is beneficial for bone calcification in the patients.  In addition, the reduced serum calcium permitted the patients to take more alfacalcidol from 2.4 ± 1.3 to 3.3 ± 1.1 µg/day in the second year.  The treatment reduced serum Bone-specific alkaline phosphatase levels, indicating improved maturation of osteoblasts and bone calcification status.  In fact, bone pain was ameliorated in these patients because of increased bone strength.  Finally cinacalcet administration increased bone mineral density in the lumbar spine by 26% and in the femur by 16%.

Although the interpretation of this study is limited by the small number of participants and absence of control subjects, our results indicate a potential new therapeutic approach for hypophosphatemic rickets/osteomalacia.