Detection and management of atypical femur fractures Purpose of review This article summarizes the risk factors for atypical femur fractures (AFF), discusses current and emerging imaging modalities for early identification of AFF, and offers recommendations for prevention and management of AFFs based on the current concepts. Recent findings Antiresorptive therapies are widely recommended for prevention and treatment of osteoporosis. Despite their well established effectiveness to reduce fracture risk, emerging concerns related to potential adverse effects have led to a substantial decline in the use of bisphosphonates. Although, the pathogenesis of AFF has not yet been elucidated, the bulk of evidence supports that the well known therapeutic benefits of bisphosphonate far outweigh the relatively low risk of AFFs. Recommendations for early identification of patients at risk for AFF using radiographic imaging have been established. Consensus on the management of AFF and osteoporosis in patients with AFF needs to be formulated. Summary AFF is a rare event associated with long-term bisphosphonate therapy, which represents an apparent paradox in the management of osteoporosis. Improved understanding of pathogenetic mechanisms will be helpful in further refining of screening guidelines and standardization of management and treatment strategies.

Combination therapies in the treatment of osteoporosis Purpose of review Osteoporotic fractures are common and can be devastating. Although multiple different medications with unique mechanisms of action are currently available in our arsenal to attempt to prevent fractures, an ideal opportunity in which to use these medications in combination remains elusive. New data has emerged over the past few years in regards to assessing which medication combinations may be productive and efficacious. Recent findings Previous studies performed using different medications to treat osteoporosis in combination proved either not overall beneficial or inconclusive. More recent studies suggest a potential additive and synergistic benefit of certain combination therapies, particularly with the use of denosumab and teriparatide in select situations. Summary The knowledge of modern data as to when the potential use of combination therapy in treating osteoporosis may be useful is critical to the acquisition of proficiency in the ideal management of our patients at highest risk for fracture. Although not recommended yet by current guidelines, the advancement of expertise in this field, both in research studies, and clinical practice, will help us discern how to best consider the use of combination treatment now and in the future.

Bone health in adult trans persons: an update of the literature Purpose of review Hormonal treatment in trans persons can affect bone health. In this review, recent studies published on this topic in adults are discussed. Recent findings Before starting hormonal treatment, trans women were found to have lower bone mineral density than cis men, which seems to be related to lower vitamin D concentrations and lower lean body mass, whereas this was not found in trans men. Short-term and long-term studies show that hormonal treatment does not have detrimental effects on bone mineral density in trans women and trans men. Low estradiol concentrations were associated with a decrease in bone mineral density in trans women. Summary Based on the reassuring findings in these studies, regularly assessing bone mineral density during hormonal treatment does not seem necessary. This confirms the Endocrine Society Guideline stating that bone mineral density should be measured only when risk factors for osteoporosis exist, especially in people who stop hormonal treatment after gonadectomy. The relationship with estradiol concentrations indicate that hormone supplementation should be adequate and therapy compliance should be stimulated. As vitamin D deficiency frequently occurs, vitamin D supplementation should be considered. Future research should focus on fracture risk and long-term changes in bone geometry.

The ongoing D-lemma of vitamin D supplementation for nonskeletal health and bone health Purpose of review The goal of this review is to give some perspective on the results and conclusions of three recent randomized controlled vitamin D intervention studies that have challenged the health benefit of vitamin D supplementation for reducing risk for cardiovascular disease, cancer, all-cause mortality and type 2 diabetes and improving bone health. Recent findings Vitamin D supplementation to adults who were vitamin D sufficient or insufficient did not reduce risk for developing cardiovascular disease, cancer, type 2 diabetes nor increases bone mineral density (BMD). Patients who were vitamin D deficient with cancer and received vitamin D reduced risk for mortality by 25% and prediabetic adults who were vitamin D deficient and received vitamin D reduced their risk of developing type 2 diabetes by 62%. Older adults receiving 4000 and 10 000 IUs of vitamin D3 daily for 3 years had reduced radial BMD but had no change in either total hip areal bone density or bone strength in the radius and tibia. Summary Caution is needed when evaluating results and conclusions from randomized controlled trials that investigate health benefits of vitamin D; most studies suggest health benefits when vitamin D supplementation is provided to vitamin D deficient populations and little benefit when given to populations that are vitamin D sufficient/insufficient.

Does night work affect age at which menopause occurs? Purpose of review To delineate the current state of evidence on the impact of night shift work on age at natural menopause. Recent findings The only direct evidence is from a single observational study, which indicates that women who work night shifts are at moderately higher risk for earlier menopause and that this risk is more pronounced among younger women. Underlying biological mechanisms have yet to be sufficiently substantiated. A long-held line of inquiry, most strongly propagated by the observed link between night shift work and female breast cancer, is the ‘Light at Night’ hypothesis, which suggests melatonin-mediated circadian disruption as a potential regulator of reproductive signaling in women. Supporting evidence is found from observations of changes in endogenous melatonin production among night working women or in response to light exposure, and corresponding changes in endogenous ovarian hormone levels and modulated menstrual patterns, among other indications of altered central ovulation-governing processes. Susceptibility to night shift work may be modified by chronotype. Summary This review summarizes the literature related to night work and ovulatory regulation in humans, prioritizing population-based evidence to provide motivation for the study of circadian disruption and night shift work as a regulator of menopausal timing.

The role of circadian rhythm in male reproduction Purpose of review To integrate evidence on the role of circadian rhythm in male reproduction. Several studies report on various aspects of the association between the circadian system and male reproductive function in animals and humans both in physiological condition as well as in the case of subfertility. Recent findings Epidemiological data demonstrate diurnal and seasonal changes as well as the effect of sleep/wake cycles on the quality of semen. Rare and common genetic variation in circadian clock genes in humans and animal models support the role of circadian rhythms in male fertility in humans. Summary Current data support the modest effect of the circadian clock on male reproductive potential; however, the evidence available is still fragmented and inconclusive. Additional well designed and sufficiently powered studies are needed to delineate the role of the circadian clock both in cause and potential interventional and preventive approaches in male subfertility.

Impact of circadian rhythms on female reproduction and infertility treatment success Purpose of review In recent years, new studies have investigated the role and influence of sleep on female fertility and early pregnancy outcomes, providing a growing body of knowledge demonstrating how regulation by sleep of hormones are important to reproduction, and how disruptions in sleep, circadian rhythms, and genes regulating circadian rhythmicity can negatively impact fertility and early pregnancy outcomes. This review aims to summarize the most recent research on the relationship among circadian rhythms, fertility, and early pregnancy outcomes in women, and to explore possible fertility interventions. Recent findings Recent studies have found altered levels of FSH, LH, and prolactin with sleep disturbance or circadian dysrhythmia. Disruption of circadian rhythms in the form of shift work, jet lag, and daylight savings time changes have been associated with poorer fertility and early pregnancy outcomes. Alterations in the expression of circadian rhythm-regulating circadian locomotor output cycles kaput (CLOCK) genes have been associated with decreased fertility and increased rates of miscarriage. Summary Overall, undisrupted sleep and circadian rhythmicity appear to optimize fertility and early pregnancy outcomes and may play an important role in the success of fertility treatment.

The inter-relationship between marginal vitamin D deficiency and muscle Purpose of review We review the recent literature on the interplay between mild vitamin D deficiency and skeletal muscle strength and performance. Recent findings Preclinical studies indicate that vitamin D is important in muscle proliferation, differentiation and mitochondrial function, whereas some epidemiological studies demonstrate associations with muscle strength and low physical performance. Recent studies have implicated vitamin D deficiency in the development of frailty and sarcopenia in the older population. Some small studies have assessed its impact on muscle function in special circumstances such as elite sport and critical illness. Advances in liquid chromatography/mass spectrometry technologies have allowed the inter-relationships between the vitamin D metabolome and muscle phenotype to be characterized. There is evidence of distinct effects on human skeletal muscle gene expression between vitamin D metabolites. Summary Large-scale clinical trials with well defined cohorts and outcomes are needed to provide clinically meaningful insights into this area. Care should be taken to stratify participants by vitamin D status at baseline and over follow-up in addition to observing a range of measures of muscle function.

Paget's disease of bone: updates for clinicians Purpose of review To provide clinicians an overview to the diagnosis, treatment, and management of Paget's disease, including recent guideline recommendations, with comparison of the Endocrine Society Clinical Practice Guideline (JCEM 2014) with the new Clinical Guideline review endorsed by the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the European Calcified Tissues Society, and the United Kingdom Bone Research Society (JBMR 2019). Recent findings Radionuclide bone scans are recommended for assessing the extent of Paget's disease. Bisphosphonates remain the mainstay for therapy with evidence of reducing symptomatic bone pain. One 5 mg intravenous dose of zoledronic acid is the current standard therapy for Paget's disease. Summary Paget's disease of the bone is characterized by focal increased bone remodeling activity, resulting in sclerotic or lytic lesions and poor bone quality at one or more sites. Patients may be symptomatic with bone pain, or may be asymptomatic, and identified through unexplained elevations in serum alkaline phosphatase. Diagnosis is through plain film imaging, with radionuclide bone scan to determine the extent. A single dose of IV zoledronic acid typically results in extended suppression of bone turnover and amelioration of bone pain. There remains a lack of evidence regarding efficacy of this treatment with regards to other complications of Paget's, but in general, bisphosphonate treatment is recommended.