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Aim: To investigate the kinetics and magnitude of human bone strontium uptake and retention during and after long-time treatment with strontium ranelate (SrR)., Methods: Bone strontium was measured by a novel DPA method developed by us. 32 osteoporotic female patients volunteered to participate in a 3 years open study of the effect on bone Sr. The group was treated with 2 g SrR/day, 17 of the group had received active treatment for 4-5 years before the study. DXA BMD measurements and DPA measurements of the relative bone strontium hydroxy apatite termed %Sr (SrHA/(CaHA+SrHA)) were done simultaneously ultra-distally (UD) on the non-dominant radius every six months during the study and three and six months after treatment stop., Results: The highest relative Sr content was found in patients who had been treated for 7-8 years. The variability was pronounced; a mean of 1.1 % Sr was measured at the end of treatment. No effect was demonstrated on distal radius relative bone Ca hydroxy apatite. Bone strontium uptake and retention data were compatible with a power function model. Withdrawal of SrR resulted in a decline in bone Sr, but 73 %Sr and 67 %Sr, respectively remained in UD-radius three and six months after drug withdrawal., Conclusion: The rise in bone Sr content measured by DPA as well as BMD measured by DXA was most marked initially. After the treatment was stopped bone Sr decreased rapidly only during the first months. In UD-radius the apparent BMD corrected for the influence of %Sr measured by DPA showed a slight decline like in an untreated population. Strontium containing drugs may influence DXA bone mineral measurements several years after treatment withdrawal. According to the power function model the skeletal retention three and six months after stopping the treatment would average 66% and 58%, respectively after three years of treatment, and 76% and 70%, respectively after eight years of treatment. However, individual predictions are uncertain due to large inter-individual variations, and the values cannot be extrapolated to other bone sites.

beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study. Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture risk (OR(adj) 3.3; 95% CI: 1.1-9.4). Analyses on duration of treatment showed that women who had been treated for more than 8 years had a higher fracture risk (OR(adj) 5.3; 95% CI: 1.1-26.3) than those treated for less than 8 years (OR(adj) 2.4; 95% CI: 0.6-9.5). In addition, cross-sectional data showed 20% lower serum osteocalcin levels (an osteoblastic marker of bone formation) in women treated with beta-blockers compared to untreated women (P < 0.001), whereas BMD at the lumbar spine and femoral neck did not differ between groups. beta-Blockers may decrease the activity of bone-forming cells and thereby increase fracture risk. However, confirmative studies and studies exploring mechanisms of action are needed.

Objective: To study 10 years compliance with oral hormonal replacement therapy (HRT)., Methods: One hundred and fifty-one early postmenopausal women were initially randomly allocated to three groups in a double blind, 2-year placebo controlled trial. Fifty women received continuous combined therapy, 50 were placed on sequential therapy, while the last 51 women were given placebo for 2 years and after that no therapy. After the trial, the women were followed in an open investigation for a total of 10 years., Results: One hundred and twenty-six women (83%) out of 151 came to a 10-year interview, 4% had died and the remaining did not want to participate. None of the women in the combined group had changed to other regimens (42% were still in treatment after 10 years). Twenty-four percent from the original sequential group were still in sequential therapy; another 24% of the group had changed to other HRTs (mainly because the women disliked the monthly bleedings). Fifty-three percent of the women from the placebo group had not received any HRT. Eighteen percent were on HRT. Eighty-seven percent of the women who had taken combined therapy for 8 years were still being treated at the tenth years' visit., Conclusion: Long-term compliance was excellent for continuous combined therapy and better than for sequential after 10 years.

In a prospective, controlled, comprehensive cohort trial of 2,016 healthy early postmenopausal women aged 45-58 years we studied fracture prevention through the use of oestrogen. There were two main study arms: a randomised arm (randomised to HRT [n = 502] or not [n = 504]) and a non-randomised arm (on HRT [n = 221] or not [n = 789] by own choice). After five years, an intention-to-treat analysis (n = 2,016) showed a reduction in the overall fracture risk (RR = 0.73, 95% CI: 0.50-1.05) and in the forearm fracture risk (RR = 0.45, 95% CI: 0.22-0.90) with oestrogen. Restriction of the analysis to women who had adhered to their initial allocation of either oestrogen (n = 395) or no oestrogen (n = 977) showed a significant reduction in both the overall fracture risk (RR = 0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR = 0.24, 95% CI: 0.09-0.69). We conclude that it is possible to reduce the number of forearm fractures in early postmenopausal women by the use of oestrogen as primary prevention.

We conducted this study to assess the prevalence of vitamin D insufficiency in a population of normal perimenopausal women, to examine the influence of sun exposure and vitamin D intake on the concentration of 25-hydroxyvitamin D (25OHD) and to examine the association between parathyroid hormone (PTH) and 25OHD. A total of 2016 healthy women aged 45-58, who had recently undergone a natural menopause, were enrolled over a 2.5-year period in the Danish Osteoporosis Prevention Study. A marked seasonal fluctuation of 25OHD was seen, with an abrupt rise in June and high values until October. The fluctuation could be related to number of hours of sunshine per month with a two months time lag. Dietary vitamin D intake, vitamin supplementation, sunlight exposure, and use of sun-bed were all significantly related to 25OHD concentrations. Sun exposure seemed to contribute the most. The overall prevalence of vitamin D deficiency (defined as serum ) was 7 %. However, in the subgroup avoiding direct sunshine and abstaining from vitamin D supplementation 32.8 % were vitamin D deficient in the winter-spring period. Although mean PTH was increased in the group with low serum 25OHD, PTH was not a sensitive marker of hypovitaminosis D in the individual, as only 16 % of those with vitamin D deficiency had PTH levels above normal range. Thus, we have shown, that healthy middle-aged Danish women are prone to vitamin D insufficiency in the winter-spring period, if they avoid sun exposure in the summer period and abstain from vitamin D supplementation.

Objectives: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario., Methods: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women., Results: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years., Conclusions: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

1. The influence of pregnancy, lactation and weaning on bone mineral density in healthy women was investigated during a 2 year prospective study of 59 pregnant and lactating women from the 18th week of gestation. 2. Bone mineral density was measured by dual energy X-ray absorptiometry at the non-dominant radius ultra distally and more proximally in the 18th and 37th weeks of gestation, and 0, 3, 6, 12 and 18 months after delivery. Measurements of bone mineral density of the lumbar spine, the proximal femur and the whole body were performed at all dates after delivery. 3. Reappearance of menstruation after delivery averaged 6.1 months; mean lactating period was 8.7 months. During pregnancy and lactation bone mineral density tended to decrease, but different measuring sites showed different patterns of bone mineral density changes. The reduction in the ultra distal radius during pregnancy amounted to 2%, and no further changes were observed here during lactation. After delivery, reduction in mean bone mineral density was most pronounced in the spine (5.2% in 3 months), but the fall in bone mass tended to revert after resumption of menstruation. Bone mineral density was still reduced by 3.3% after 12 months in women with menstruation resumption later than 8 months after delivery. No significant reduction was observed 18 months after delivery. No association with calcium intake, weight changes or initial bone mineral density was observed. High calcium intake did not protect against bone mineral loss in the spine and the femur. 4. Thus it can be concluded that bone loss during pregnancy and lactation took place mainly from the trabecular skeleton. Resumption of menstruation tended to result in a regain of bone mass towards baseline.

Objective: The purpose of this randomised double-blind placebo-controlled study over two years followed by a six year open controlled extension phase was to investigate the effects of hormonal replacement therapy (HRT) both continuous combined HRT and sequential HRT) versus no treatment on lumbar spine bone mineral density (L-BMD) and distal forearm bone mineral content (F-BMC). Further, bone mineral density of the proximal femur, lateral spine, and distal forearm was studied after eight years., Design: Prospective study of normal, early postmenopausal women, initially in a double-blind, placebo controlled study, subsequently an open, controlled investigation., Setting: Clinical physiology unit of a general second degree referral hospital., Sample: Seventy-three normal, early postmenopausal women (HRT n = .47; placebo/untreated n = 26)., Methods: Dual photon absorptiometry, dual X-ray absorptiometry, single photon absorptiometry., Main Outcome Measures: HRT resulted in a significantly (P < 0.001) higher mean L-BMD after eight years, when it was 12.1% higher than the mean initial value and 14.8% higher than the mean bone mineral density of the untreated group. L-BMD increased by 14.6% in women receiving continuous combined HRT compared with 11.1% in those on sequential HRT but intergroup differences were not statistically significant. Mean F-BMC measured with SPA decreased in the HRT group and in the placebo/untreated group by 0.2% and 14.8% (P < 0.001), respectively. However, after eight years mean F-BMC was 14.5% higher in the HRT group than in the placebo/untreated group. The study showed after eight years for all regions of the distal radius and ulna a significantly higher bone mineral density value compared with the placebo/untreated group (P < 0.001). An especially large effect of HRT was found on the bone mineral density of the vertebral body of the 3rd lumbar vertebra (L3), this one, measured by lateral scanning, being 18.7% higher than that of the placebo/untreated group. For the proximal femur, only the bone mineral density of Ward's triangle was significantly higher in the HRT group than in the placebo/untreated group., Conclusion: Eight years of treatment with HRT resulted in a significant, substantial gain of bone mineral density in the lumbar spine. The distal radius, ulna and Ward's triangle showed a significantly higher bone mineral density in the HRT group compared with the placebo/untreated group.