The effect of intermittent administration of 200 IU intranasal salmon calcitonin and low doses of 1α (OH) vitamin D3 on bone mineral density of the ;i,bar s[ome and hip region and biochemical bone markers in women with postemenopausal osteoporosis

The purpose of this prospective open randomized controlled study was to examine the effect of cyclical administration of 200IU intranasal salmon calcitonin in combination with 0,25μg alfacalcidol and calcium 500mg given continuously, on bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) method, on quantitative and qualitative determinants of bone quality measured by peripheral quantitative computed tomography (pQCT) method and on biochemical markers of bone turnover in women with postmenopausal osteoporosis over a period of one year. A total of 102 randomly assigned women received either 200IU nasal salmon calcitonin (Miacalcic nasal 200, Novartis, Basle, Switzerland), daily for alternative cycles of one month with one month interval, 500mg elemental calcium and 0,25μg alfacalcidol continuously (group 1: n= 57 women, mean age 59.7 years), or only 500mg calcium and 0.25 μg alfacalcidol (group 2: n= 45 women, mean age 58.95 years). Bone mineral density (BMD) of the lumbar spine and hip by DXA method, pQCT method at the non-dominant forearm (4% and 20% area) and biochemical parameters reflecting calcium metabolism and bone turnover (serum calcium, phosphorus, intact parathormone (iPTH), total and bone specific alkaline phosphatase and osteocalcin levels, 24-h urinary calcium and morning fasting urinary calcium/creatinine, and pyrilinks-D/creatinine ratio) were performed at baseline, 6 and 12 months. Baseline characteristics of participants including age, body mass index, lumbar and hip BMD, pQCT values at the distal and the proximal side of the radius (4% and 20% areas respectively) and biochemical markers were similar among the two groups. Ninety one patients (87%) completed the study. Eleven women (7 in the salmon calcitonin nasal spray group and 4 in the other group) were excluded from the study due to bad compliance. Lumbar bone mineral density was increased significantly in the salmon calcitonin group compared with baseline values at 12 months (3.0%, p<0.001) and in comparison with the other group (p=0.009). Salmon calcitonin group had also a significant increase in femoral neck BMD compared with baseline values (3.1%, p=0.0005) and in comparison with the other group (p<0.0005), in Ward’s triangle BMD (2.9% compared with baseline values: p=0.009 and in comparison with the other group: p=0.005) and in trochanter BMD (3.38% compared with baseline values: p<0.001 and in comparison with the other group: p=0.01). Salmon calcitonin group patients showed preservation of pQCT values at the distal site of the radius (4% area) for the trabecular density and content (BMDtrab = 0.33% and BMCtrab= 1.5%), in comparison with the non calcitonin treated group which showed decrease of the above values (BMDtrab -4.88%, p<0.001 compared with baseline values and p<0.05 compared with calcitonin treated group and BMCtrab -5.06% ,p<0,001 compared with baseline values and p<0,05 compared with calcitonin treated group ) and preservation of total content (BMCtot) compared with baseline values and in comparison with the non calcitonin treated group which showed decrease of the above value ((p<0.001 compared with baseline values and p<0.05 in comparison with the calcitonin treated group). At the proximal site of the radius (20% area) which is characterized by the domination of cortical and the absence of trabecular bone, the calcitonin treated group at 12 months preserved subcortical density and content (BMDsub -1.24% and BMCsub -0.77%) in comparison with the non calcitonin treated group which showed decrease of the above values (BMDsub -8.10%, p<0.001 compared with baseline values and p<0.05 in comparison with the calcitonin treated group, BMCsub -4.14%, p<0,001 compared with baseline values and p<0,05 in comparison with the calcitonin treated group). The non calcitonin treated group showed decrease of the cortical area, density and content (CSAcort p<0.01 and BMDcort, BMCcort p<0.001 for both comparisons) and of the Stress/Strain Index in torsion (SSIp) (p<0.01) at 12 months compared with baseline values but not in comparison with the calcitonin treated group. In the salmon calcitonin treated group there was a significant decrease in PTH serum levels compared to baseline (-2,5%, p=0.005) and in comparison with the other group (p=0,03). At 12 months 24-h urinary calcium levels were increased in the salmon calcitonin treated group (3.0 p<0.05) compared with baseline values, but not in comparison with the other group. Total and bone specific alkaline phosphatase levels were decreased significantly at 12 months compared with baseline values in the salmon calcitonin treated group (-1.7% p< 0.05 and -3.62%, p=0.003 respectively) but not in comparison with the other group