Effect of etidronate disodium on bone turnover following surgical menopause

Summary A longitudinal study was performed to document the effect of surgical menopause and postmenopausal etidronate disodium therapy on several nonhistomorphometric indices of bone turnover. Twenty healthy, premenopausal women undergoing oophorectomy for nonmalignant conditions were studied preoperatively and at 3 monthly intervals postoperatively. Sequential measurements of serum calcium (Ca), alkaline phosphatase (AP), bone Gla protein (BGP), and urinary calcium and hydroxyproline excretion, expressed as a ratio of urinary creatinine (UCa/Cr and UOHp/Cr, respectively) were obtained. Twenty-four-hour whole body retention of diphosphonate (WBR) and radial bone density were also measured. When a postoperative increase in bone turnover was observed, patients were randomized to receive either 400 mg etidronate disodium daily or placebo for 3 months. Oophorectomy was associated with a significant increase in WBR, Ca, AP, and BGP and an insignificant rise in UCa/Cr. A variable pattern of UOHp/Cr was seen. Patients on placebo maintained these elevated levels of Ca, BGP, and UCa/Cr. WBR and AP continued to rise. Etidronate disodium therapy resulted in a fall towards premenopausal levels in WBR, Ca, and UCa/Cr. AP and BGP were unchanged. Three months after stopping etidronate, BGP fell significantly and the decrease in Ca was maintained; however, WBR and UCa/Cr had returned towards pretreatment values. Bone density measurements did not change significantly. An increase in several of the indices of bone turnover was seen following oophorectomy. Etidronate disodium suppressed this increase, affecting indices of both resorption and formation. This effect on formation may be an unavoidable consequence of normal resorption-formation coupling. The ability of etidronate alone to maintain postmenopausal bone mass has yet to be established. However, the suppressive effect of this diphosphonate on the accelerated bone turnover found after oophorectomy suggests that etidronate may have a potentially useful role as an inhibitor of resorption in a pulsed regimen.