Clinical Investigations Suppression of Bone Resorption in Early Postmenopausal Women by Intranasal Salmon Calcitonin in Relation to Dosage and Basal Bone Turnover B. Ongphiphadhanakul, N. Piaseu, L. Chailurkit, R. Rajatanavin Department of Medicine, Ramathibodi Hospital, Mahidol University, Rama 6 Rd., Phya Thai, Bangkok 10400, Thailand Received: 10 March 1997 / Accepted: 14 November 1997 Abstract. In the present study, we assessed the ability of increasing doses of intranasal calcitonin to suppress urinary deoxypyridinoline cross-link (DPD), a specific biochemical marker of bone resorption, in early postmenopausal women. Subjects consisted of 30 healthy Thai women within 5 years of postmenopause, randomly assigned to 50, 100, or 200 IU of intranasal calcitonin 5 days/week for 3 months. Calcium supplementation by calcium carbonate capsules at 750 mg of elemental calcium per day was given to all subjects. Twenty four-hour urine for DPD and creatinine assays was collected at baseline, 1 month, and 3 months after treatment. All DPD values were corrected with urinary creatinine be- fore analyses. Data were expressed as mean ± SEM. DPD decreased significantly 1 month after intranasal calcitonin treatment (P < 0.01). However, at 3 months, DPD increased when compared with the values at 1 month (P < 0.01), suggesting that there may be a reduction in the suppression of bone resorption after prolonged calcitonin therapy. Using a stepwise multiple regression model to address whether dosage and DPD at baseline influence the response to in- tranasal calcitonin, it was found that DPD suppression after intranasal calcitonin was not related to dosage but was strongly associated with baseline DPD (P < 0.0001). Sup- pression of bone resorption in early postmenopausal women by intranasal calcitonin is determined more by the state of bone turnover at baseline than the dosage of calcitonin. Key words: Salmon calcitonin — Osteoporosis — Bone turnover — Menopause — Dosage study. Calcitonin has been reported to be effective in preventing bone loss and to decrease vertebral fractures in postmeno- pausal women with osteoporosis [1–3]. It acts through spe- cific calcitonin receptors on osteoclasts [4] and this is re- flected in the decrease of biochemical markers of bone re- sorption in subjects on calcitonin [5]. Although effective, calcitonin needed to be administered by intramuscular or subcutaneous injection until recently when intranasal calci- tonin became available. Similar to the results from calcito- nin injection, intranasal calcitonin has been shown to be effective in the retardation of bone loss and decrease in vertebral fractures in patients with osteoporosis [3]. Immediately after menopause, bone loss occurs at an accelerated rate largely because of estrogen deficiency [6–8]. Estrogen replacement is considered to be the thera- peutic intervention of choice for preventing postmenopausal bone loss. However, a number of postmenopausal women are unable to take estrogen because of the side effects, es- pecially vaginal bleeding [9]. Increased risk for endometrial cancer with unopposed estrogen has been well documented. Moreover, potential risk of breast cancer is another con- straint especially in subjects with family or previous history of breast cancer. Besides estrogen, alendronate [10] and intranasal calcitonin [11–14] have been shown to be effec- tive in the reduction of bone loss during early postmeno- pausal years. Appropriate doses of intranasal calcitonin for this purpose vary widely among studies—from 50 to 400 IU. The reasons for this inconsistency are unclear. Since intranasal calcitonin is relatively expensive, we attempted to find the minimal effective dose within 5 years of postmeno- pause by examining the dose-response relationship of intra- nasal calcitonin in the retardation of bone resorption. The probable effect of basal bone turnover on the response to calcitonin was also addressed. Materials and Methods Subjects consisted of 30 healthy Thai women within 5 years of postmenopause, recruited by flyers or advertisement. History tak- ing and complete physical examination were performed on each subjects. All were considered to be healthy and were not taking medications that may affect calcium and bone metabolism. The study was approved by the ethical clearance committee on human rights related to research involving human subjects of the Faculty of Medicine, Ramathibodi Hospital, Mahidol University. The subjects were randomly assigned to self-administer 50 IU, 100 IU, or 200 IU of intranasal salmon calcitonin (Sandoz, Swit- zerland) 5 days/week for 3 months. Each subject also took calcium supplementation in the form of calcium carbonate capsules at a dose of 750 mg of elemental calcium per day. Twenty-four-hour urine for deoxypyridinoline cross-link (DPD) and creatinine assays were collected at baseline, 1 month, and 3 months after treatment. Correspondence to: B. Ongphiphadhanakul Calcif Tissue Int (1998) 62:379–382 © 1998 Springer-Verlag New York Inc.