Raloxifene reverses bone loss in postmenopausal women with mild asymptomatic primary hyperparathyroidism.

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RALOXIFENE IS a selective estrogen receptor modulator (SERM) acting as a tissue-specific estrogen receptor agonist on bone and lipid metabolism and as an estrogen antagonist in the breast and uterus, currently approved for both prevention and treatment of postmenopausal osteoporosis in the United States and Europe. It has been shown to reduce the incidence of vertebral fractures1 and of breast cancer1 in osteoporotic women. Here, we report the effects of 12 months of treatment with raloxifene, 60 mg/day or 120 mg/day, on lumbar spine and femur neck bone mineral density (BMD) and biochemical parameters in 3 postmenopausal osteopenic women (mean age, 64; range 59–67 years; mean lumbar spine T score, −1.92) with mild, asymptomatic primary hyperparathyroidism. Patients were experiencing rapid bone loss during the last 2 years (Fig. 1). Treatment with raloxifene was considered because they refused either parathyroid surgery or hormone replacement therapy. Options and treatment characteristics were discussed with the patients and they gave their consent to treatment. Mean percentage change in lumbar spine (solid circles) and femur neck (open circles, dashed lines) BMD before therapy and after 12 months of raloxifene treatment in postmenopausal women with mild, asymptomatic primary hyperparathyroidism. Error bars denote SD. BMD increased by 3.4% at lumbar spine and by 2.5% at femur neck after 12 months of treatment (Fig. 1). The effects of treatment on biochemical parameters are shown in Table 1. Total calcium and phosphate levels decreased in all the patients after 12 months of treatment. On the other hand, ionized calcium and intact parathyroid hormone (iPTH) levels showed a decrease after 6 months of treatment, but returned close to baseline values at month 12. Deoxypyridinoline excretion, a specific marker of bone resorption, decreased by 33% after 6 months and by 61% after 12 months; fasting calcium excretion was 39% lower at 6 months and 56% lower at 12 months. Serum total alkaline phosphatase, a marker of osteoblast function, showed only a slight decrease. The apparently different effects of raloxifene on serum total and ionized calcium levels found in our patients also has been noted with hormone replacement therapy in both postmenopausal women with mild primary hyperparathyroidism2 and normal, early postmenopausal women.3 Therefore, it is possible that raloxifene would decrease only the complexed fraction of serum calcium, as estrogen does.4 To our knowledge, there are no published data on the effect of raloxifene on parathyroid function, and the effect of estrogen therapy on PTH levels in postmenopausal women with primary hyperparathyroidism is controversial. In a small, preliminary study on hormone replacement therapy in postmenopausal women presenting with primary hyperparathyroidism, Diamond et al.5 reported no changes in PTH levels during treatment. In contrast, Gray et al., in a randomized, controlled trial,2 showed that hormone replacement therapy significantly increases circulating iPTH levels in postmenopausal women with mild primary hyperparathyroidism. However, the increase in iPTH occurred also in the placebo group. In our patients PTH levels did not increase. In fact, a transient decrease was observed after 6 months of treatment. This suggests that more careful examination of raloxifene effect on parathyroid function is needed. The decrease in biochemical markers of bone resorption and urine calcium excretion obtained with raloxifene in this study are in agreement with previous reports on the effects of raloxifene in healthy postmenopausal women6, 7 and might account for the changes observed in BMD. In summary, our preliminary results suggest that raloxifene may be an alternative treatment for preventing bone loss in postmenopausal osteopenic women with mild, asymptomatic primary hyperparathyroidism. Larger, controlled studies aimed to confirm the safety and efficacy of raloxifene treatment in this group of patients are warranted. This work was supported by funds from the Fundacion de Investigaciones Metabolicas, Buenos Aires, Argentina.