No abstract

Transdermal hormone replacement therapy (HRT) is now an accepted form of treatment, but the long-term skeletal effects have not been assessed. Sixty-six early postmenopausal women were randomized to receive either transdermal HRT (continuous 17 beta-oestradiol 0.05 mg/day, with 0.25 mg/day of norethisterone acetate added for 14 days of each 28-day cycle) or oral HRT (continuous conjugated equine oestrogens 0.625 mg/day, with 0.15 mg/day dl-norgestrel added for 12 days of each 28-day cycle). Treatment was given for 3 years and 30 matched untreated women were studied concurrently as a control group. Bone density was measured in the lumbar spine and proximal femur by dual-photon absorptiometry at 6-monthly intervals. Bone turnover was assessed by measurement of biochemical markers. At 3 years bone density had declined by 4% in the lumbar spine and by more than 5% in the femoral neck in the untreated group. By comparison bone density increased in both treatment groups at both sites (p < 0.001 vs. untreated) and biochemical measurements indicated a significant reduction in bone turnover. There were no significant differences between the treatment groups. Twelve per cent of women on transdermal or oral treatments lost a significant amount of bone from the femoral neck by 3 years despite adequate compliance. Women taking therapy primarily for hip fracture prevention may require a follow-up bone density measurement to establish the efficacy of treatment.

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/ progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.