Bone turnover in postmenopausal osteoporosis. Effect of calcitonin treatment.

UNLABELLED: To investigate the effectiveness of calcitonin treatment of postmenopausal osteoporosis in relation to bone turnover, we examined 53 postmenopausal osteoporotic women before and after one year of therapy with salmon calcitonin (sCT), at the dose of 50 IU every other day. Baseline evaluation revealed that 17 (32%) patients had high turnover (HTOP), and 36 (68%) normal turnover osteoporosis (NTOP) as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. The two groups did not differ in terms of bone mineral content (BMC) measured by dual photon absorptiometry at both lumbar spine and femoral diaphysis. However, HTOP patients had higher levels of serum osteocalcin (OC) and urinary hydroxyproline excretion (HOP/Cr). Multivariate regression analysis showed no correlation between parameters of bone turnover (WBR, OC, HOP/Cr) and both femoral and vertebral bone density; the latter being negatively correlated only with the years elapsed since menopause (R2 = 0.406). Treatment with sCT resulted in a significant increase of vertebral BMC in the 53 patients taken as a whole group (+/- 7%, P less than 0.001). When the results obtained in HTOP and NTOP were analyzed separately, only those with HTOP showed a marked increment of spinal BMC (+22%, P less than 0.001), NTOP subjects neither gained nor lost bone mineral during the study. Femoral BMC decreased in the whole group after sCT therapy (-3%, P less than 0.003). However, HTOP patients maintained initial BMC values, whereas those with NTOP lost a significant amount of bone during the study period (-5%, P less than 0.001). The increase of vertebral bone mass was associated with a marked depression of bone turnover detectable in both subsets of patients and in the whole group. IN CONCLUSION: (a) assessment of bone turnover cannot help predict the severity of bone loss in postmenopausal osteoporosis; (b) calcitonin therapy appears to be particularly indicated for patients with high-turnover osteoporosis, resulting in a net gain of bone mineral in the axial skeleton and a slowing of bone loss in the appendicular bones.

Serum osteocalcin concentration in patients with prostatic cancer.

Fifty-four subjects were studied: 36 advanced prostatic adenocarcinoma patients in stage D and 18 normal age-matched male controls. Serum alkaline phosphatase, serum acid phosphatase, plasma osteocalcin, 24-h urinary hydroxyproline excretion, and 24-h whole-body retention of [99mTc]-methylene diphosphonate were measured in all subjects before and 3, 6, and 9 weeks after the start of treatment. Skeletal metastases were identified by radiography and/or [99mTc]-methylene diphosphonate bone scan. The results confirm that acid phosphatase is a significant marker in prostatic cancer; serum alkaline phosphatase may be useful in the evaluation and monitoring of bone metastases but it is not always specific; urinary excretion of hydroxyproline is an index of osteoclastic activity; serum osteocalcin may be considered more specific in the evaluation and monitoring of osteoblastic bone metastases in prostatic cancer.

Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis.

Twenty patients with post-menopausal osteoporosis were randomly divided into two groups of ten patients and treated under double-blind conditions with ipriflavone (Osteofix) or placebo. The dosage was 600 mg/day given in three doses and treatment lasted 6 months. All the patients received an oral calcium supply (1 g per day). At baseline and then after 3 and 6 months, the following parameters were controlled: bone mineral content at the lumbar spine, distal radius and femoral shaft; parameters of bone metabolism (alkaline phosphatase, PTH, osteocalcin, calcitonin, calciuria and hydroxyprolinuria); clinical conditions (pain at rest and on movement, motility). Ipriflavone facilitated the conservation of bone mass, that increased in one of the tested areas (distal radius). On the contrary, a bone mineral loss was found in the group treated with placebo, which was significant in the spine. Pain and motility significantly improved in the group treated with ipriflavone; there was an initial improvement in the control group, followed by a sharp worsening. The parameters investigated showed a significant reduction of osteocalcin in the ipriflavone group that indicates a modulation on bone turnover. The drug was well tolerated and compliance to oral treatment was excellent.

[Calcitonin, parathyroid hormones, calcium ion, cyclic 3,5-adenosine monophosphate (cAMP) and erythrocyte deformability]. / Calcitonina, ormone paratiroideo, ione calcio, 3,5-adenosinmonofosfato ciclico (AMPc) e deformabilità eritrocitaria.

Calcium ion is one of the factors which modulate erythrocyte deformability. It is known that calciotropic hormones such as calcitonin (CT) and parathyroid hormone (PTH) exert hypocalcemizing and hypercalcemizing effects, respectively. Their action is mediated, at the level of their target cells, through adenylcyclase activation with the production of cyclic 3,5-adenosinmonophosphate (cAMP). Modifications of transmembrane calcium fluxes have been described and were attributed to these hormones. Erythrocyte deformability has been evaluated by Dormandy method of red blood cell filtration in hypocalcemic patients affected by hypoparathyroidism, in patients with hypercalcemia due to malignancy or primary hyperparathyroidism and in normal age- and sex-matched subjects. Erythrocyte filtration values resulted to be significantly increased with respect to normal values in hypercalcemic patients and at the lower limits of normality in hypocalcemic subjects. Subsequently, acute studies were performed in normal volunteers in whom venous infusions of synthetic salmon calcitonin determined a significant reduction of erythrocyte filtration values, whereas venous infusions of the 1-34 synthetic human PTH fragment induced a significant increase in filtration values of red blood cells. An infusion of a cAMP analogue, dibutyryl-cAMP, determined a slight reduction of erythrocyte filtration values. The calciotropic hormones influence erythrocyte deformability through mechanisms that are yet to be clarified.