Current pharmacological options for the management of primary hyperparathyroidism

Drugs for treating primary hyperparathyroidism can be divided into two main groups: (i) antiresorptive drugs that inhibit the increased bone turnover, which can be divided into estrogen-like compounds (estrogen, oral contraceptives and selective estrogen receptor modulators [SERMs]), bisphosphonates and calcitonin; and (ii) drugs that interfere with parathyroid hormone (PTH) secretion (currently only cinacalcet is available). No drugs that interfere with PTH action are currently available. Available studies suggest that all classes of drugs are able to lower serum calcium levels. However, calcitonin does so only temporarily. Estrogen-containing compounds (hormone replacement therapy) may be less attractive because of the potential risk of breast cancer, cardiovascular disease and deep vein thromboembolism. Oral contraceptives have not been shown to be able to prevent fractures in the general population, and no data are available on their effect in women with primary hyperparathyroidism. The only SERM marketed for hyperparathyroidism is raloxifene and this has not been associated with an increased risk of breast cancer and cardiovascular diseases, and has been shown to be able to prevent vertebral fractures in postmenopausal women with osteoporosis. Two small trials suggest that raloxifene may increase bone mineral density (BMD) and decrease serum calcium levels in patients with primary hyperparathyroidism. Bisphosphonates have been shown to decrease serum calcium and increase BMD in patients with primary hyperparathyroidism, but PTH levels may increase. Cinacalcet effectively induces a sustained decrease in serum calcium and PTH for up to 1 year. However, BMD does not seem to increase. No data on hard endpoints such as fractures, kidney stones, cardiovascular disease etc. are available for any of the drugs available for the treatment of primary hyperparathyroidism.