Calcitonin likely reduces the risk of vertebral fracture; however, the magnitude of the impact on these fractures remains questionable [175]. An effect on non-vertebral fractures remains equivocal [226, 227]. In addition, calcitonin may have an analgesic effect in women with acute vertebral fracture, which appears to be independent

of its effect on osteoclastic resorption [224]. In conclusion, the drawbacks of repeated injections and the high costs of the nasal formulation preclude the long-term use of calcitonin as a first line in the treatment of osteoporosis. Analgesic properties may, however, be an interesting option for acute pain following a spinal fracture. Hormone replacement therapy Oestrogens reduce the accelerated bone turnover induced by menopause and prevent bone loss at all skeletal sites regardless of age and duration of therapy. Results from buy APR-246 observational selleck kinase inhibitor studies and randomised placebo controlled trials have shown that oestrogens decrease the risk of vertebral and non-vertebral fractures (including hip fracture) by about 30 %, regardless of baseline BMD [158, 228, 229]. When hormone replacement therapy (HRT) is stopped, bone loss resumes

at the same rate as after menopause, but fracture protection may persist arguably for several years [230, 231]. The Women’s Health Initiative suggests, however, that the long-term risks of HRT outweigh the benefits. In this large cohort of postmenopausal women selleck inhibitor in their 60s, the combined use of conjugated oestrogen and medroxyprogesterone acetate was associated with a 30 % increased risk of coronary heart disease (CHD) and breast cancer, and with a 40 % increase in stroke [232–234]. There was also a slight increase in the risk of dementia [235] and no clinically meaningful effect on health-related quality of life such as sleep disturbance or vasomotor symptoms [236]. In a subsequent analysis, the increase in breast cancer risk was much less in women not previously

Temsirolimus mouse exposed to HRT [234]. In hysterectomized women receiving conjugated oestrogen alone, there was also a significant increase in stroke, but not of CHD and breast cancer, suggesting a deleterious effect of medroxyprogesterone acetate [237]. It has been postulated that the benefits of HRT outweigh the risks in younger postmenopausal women [238, 239], but so far, there is no placebo controlled study showing the long-term safety of such approaches. In most countries, HRT is only recommended for climacteric symptoms, at a dose as small as possible and for a limited period of time. Etidronate Etidronate is a weak bisphosphonate that has been shown to reduce vertebral fractures over 2 years but not subsequently, with no significant effect on non-vertebral fractures [240]. Thus, etidronate is not recommended as a first-line therapy for osteoporosis in most European countries.