HRT has a consistent, favorable and large effect on bone density at all sites. The data show a nonsignificant trend toward a reduced incidence in vertebral and nonvertebral fractures.

This section summarizes the results of the seven systematic reviews of osteoporosis therapies published in this series [calcium, vitamin D, hormone replacement therapy (HRT), alendronate, risedronate, raloxifene, and calcitonin] and systematic reviews of etidronate and fluoride we have published elsewhere. We highlight the methodological strengths and weaknesses of the individual studies, and summarize the effects of treatments on the risk of vertebral and nonvertebral fractures and on bone density, including effects in different patient subgroups. We provide an estimate of the expected impact of antiosteoporosis interventions in prevention and treatment populations using the number needed to treat (NNT) as a reference. In addition to the evidence, judgements about the relative weight that one places on weaker and stronger evidence, attitudes toward uncertainty, circumstances of patients' and societal values or preferences will, and should, play an important role in decision-making regarding anti-osteoporosis therapy.

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Alendronate increases bone density in both early postmenopausal women and those with established osteoporosis while reducing the rate of vertebral fracture over 2-3 yr of treatment. Reductions in nonvertebral fractures are evident among postmenopausal women without prevalent fractures and have bone mineral density (BMD) levels below the World Health Organization threshold for osteoporosis. The impact on fractures appears consistent across all fracture types, casting doubt on traditional distinctions between osteoporotic and nonosteoporotic fractures.

While it is important for the evidence supporting practice guidelines to be current, that is often not the case. The advent of living systematic reviews has made the concept of "living guidelines" realistic, with the promise to provide timely, up-to-date and high-quality guidance to target users. We define living guidelines as an optimization of the guideline development process to allow updating individual recommendations as soon as new relevant evidence becomes available. A major implication of that definition is that the unit of update is the individual recommendation and not the whole guideline. We then discuss when living guidelines are appropriate, the workflows required to support them, the collaboration between living systematic reviews and living guideline teams, the thresholds for changing recommendations, and potential approaches to publication and dissemination. The success and sustainability of the concept of living guideline will depend on those of its major pillar, the living systematic review. We conclude that guideline developers should both experiment with and research the process of living guidelines.