How can the orthopedic surgeon ensure optimal vitamin D status in patients operated for an osteoporotic fracture?

In this narrative review, the role of vitamin D deficiency in the pathophysiology, healing of fragility fractures, and rehabilitation is discussed. Vitamin D status can be assessed by measuring serum 25(OH)-vitamin D level with standardized assays. There is a high prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/l (i.e., 20 ng/mL)) or deficiency (25(OH)D < 25 nmol/l (i.e., 10 ng/mL)) in patients with fragility fractures and especially in those with a hip fracture. The evidence on the effects of vitamin D deficiency and/or vitamin D supplementation on fracture healing and material osseointegration is still limited. However, it appears that vitamin D have a rather positive influence on these processes. The fracture liaison service (FLS) model can help to inform orthopedic surgeons, all caregivers, and fractured patients about the importance of optimal vitamin D status in the management of patients with fragility fractures. Therefore, vitamin D status should be included in Capture the Fracture® program as an outcome of FLS in addition to dual-energy X-ray absorptiometry (DXA) and specific antiosteoporosis medication. Vitamin D plays a significant role in the pathophysiology and healing of fragility fractures and in rehabilitation after fracture. Correction of vitamin D deficiency should be one of the main outcomes in fracture liaison services.

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

Improving pregnant women's diet and physical activity behaviours: the emergent role of health identity.

BACKGROUND: Women who gain too much weight in pregnancy are at increased risk of disease and of having children with increased risk. Interventions to improve health behaviours are usually designed for a general population of pregnant women, and trial outcomes show an average impact that does not represent the differences between individuals. To inform the development of future interventions, this study explored the factors that influenced women's diet and physical activity during pregnancy and aimed to identify the needs of these women with regards to lifestyle support. METHODS: Women who completed a trial of vitamin D supplementation and nurse support in pregnancy were invited to take part in an interview. Seventeen women were interviewed about their lifestyles during pregnancy, the support they had, and the support they wanted. Interview transcripts were coded thematically and analysed to understand the factors that influenced the diets and physical activity levels of these women and their engagement with resources that could provide support. RESULTS: Women identified barriers to eating well or being physically active, and pregnancy-specific issues like nausea and pain were common. Women's interest in maintaining a healthy lifestyle and their engagement with lifestyle support was related to the extent to which they self-identified as healthy people. Health-disengaged women were disinterested in talking about their lifestyles while health-focused women did not feel that they needed extra support. Women between these ends of the 'health identity' spectrum were interested in improving their health, and were able to identify barriers as well as sources of support. CONCLUSIONS: Lifestyle interventions in pregnancy should be adapted to meet the needs of individuals with different health identities, and encouraging a change in health identity may be one way of supporting sustained change in health behaviours.

Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review.

This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified. Results indicate that physical exercise has a positive impact on muscle mass and muscle function in subjects aged 65 years and older. However, any interactive effect of dietary supplementation appears to be limited. INTRODUCTION: In 2013, Denison et al. conducted a systematic review including 17 randomized controlled trials (RCTs) to explore the effect of combined exercise and nutrition intervention to improve muscle mass, muscle strength, or physical performance in older people. They concluded that further studies were needed to provide evidence upon which public health and clinical recommendations could be based. The purpose of the present work was to update the prior systematic review and include studies published up to October 2015. METHODS: Using the electronic databases MEDLINE and EMBASE, we identified RCTs which assessed the combined effect of exercise training and nutritional supplementation on muscle strength, muscle mass, or physical performance in subjects aged 60 years and over. Study selection and data extraction were performed by two independent reviewers. RESULTS: The search strategy identified 21 additional RCTs giving a total of 37 RCTs. Studies were heterogeneous in terms of protocols for physical exercise and dietary supplementation (proteins, essential amino acids, creatine, ß-hydroxy-ß-methylbuthyrate, vitamin D, multi-nutrients, or other). In 79% of the studies (27/34 RCTs), muscle mass increased with exercise but an additional effect of nutrition was only found in 8 RCTs (23.5%). Muscle strength increased in 82.8% of the studies (29/35 RCTs) following exercise intervention, and dietary supplementation showed additional benefits in only a small number of studies (8/35 RCTS, 22.8%). Finally, the majority of studies showed an increase of physical performance following exercise intervention (26/28 RCTs, 92.8%) but interaction with nutrition supplementation was only found in 14.3% of these studies (4/28 RCTs). CONCLUSION: Physical exercise has a positive impact on muscle mass and muscle function in healthy subjects aged 60 years and older. The biggest effect of exercise intervention, of any type, has been seen on physical performance (gait speed, chair rising test, balance, SPPB test, etc.). We observed huge variations in regard to the dietary supplementation protocols. Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supplementation on muscle function appears limited.

The relationship between maternal self-efficacy, compliance and outcome in a trial of vitamin D supplementation in pregnancy.

In a randomised controlled trial of vitamin D during pregnancy, we demonstrated that women with lower self-efficacy were more likely to experience practical problems with taking the trial medication and that this was associated with lower compliance and achieved 25(OH)-vitamin D concentrations. INTRODUCTION: The relationship between self-efficacy (the belief that one can carry out a behaviour), compliance with study protocol and outcome was explored within a randomised, double-blind, placebo-controlled trial of vitamin D supplementation in pregnancy. METHODS: In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial, women with circulating plasma 25(OH)-vitamin D of 25-100 nmol/l in early pregnancy were randomised to either 1000 IU cholecalciferol/day or matched placebo from 14 weeks until delivery. Circulating 25(OH)-vitamin D concentrations were assessed at 14 and 34 weeks' gestation. A sequential sub-sample completed Schwarzer's General Self-Efficacy Scale at 14 and 34 weeks and the Problematic Experiences of Therapy Scale at 34 weeks. Women were interviewed about their experiences of the trial and interview transcripts analysed thematically. RESULTS: In 203 women, those with higher self-efficacy were less likely to experience practical problems taking the study medication (odds ratio (OR) 0.81 (95 % confidence interval (CI) 0.69-0.95), p = 0.01). Over half reported practical problems associated with poorer compliance with the protocol requiring women to take the medication daily. Compliance in women who experienced practical problems was 94 % compared with 98 % for those with no problems (p < 0.001). Poorer compliance was also associated with lower concentrations of 25(OH)-D in late pregnancy in the treatment group (ß = 0.54 nmol/l (95 % CI 0.18-0.89), p = 0.003). Thematic analysis suggested common difficulties were remembering to take the medication every day and swallowing the large capsules. CONCLUSIONS: These findings suggest that differences in self-efficacy influence trial outcomes. Such information may help clinicians anticipate responses to routine vitamin D supplementation in pregnancy and identify those who may need more support to comply. TRIAL REGISTRATION: ISRCTN82927713, registered 11/04/2008.

The role of calcium supplementation in healthy musculoskeletal ageing : An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF).

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice.

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.

Vitamin D and skeletal health in infancy and childhood.

During growth, severe vitamin D deficiency in childhood can result in symptomatic hypocalcaemia and rickets. Despite the suggestion from some studies of a secular increase in the incidence of rickets, this observation may be driven more by changes in population demographics than a true alteration to age, sex and ethnicity-specific incidence rates; indeed, rickets remains uncommon overall and is rarely seen in fair-skinned children. Additionally, the impact of less severe vitamin D deficiency and insufficiency has received much interest in recent years, and in this review, we consider the evidence relating vitamin D status to fracture risk and bone mineral density (BMD) in childhood and adolescence. We conclude that there is insufficient evidence to support the suggestion that low serum 25-hydroxyvitamin D [25(OH)D] increases childhood fracture risk. Overall, the relationship between 25(OH)D and BMD is inconsistent across studies and across skeletal sites within the same study; however, there is evidence to suggest that vitamin D supplementation in children with the lowest levels of 25(OH)D might improve BMD. High-quality randomised trials are now required to confirm this benefit.

Management of osteoporosis of the oldest old.

UNLABELLED: This consensus article reviews the diagnosis and treatment of osteoporosis in geriatric populations. Specifically, it reviews the risk assessment and intervention thresholds, the impact of nutritional deficiencies, fall prevention strategies, pharmacological treatments and their safety considerations, the risks of sub-optimal treatment adherence and strategies for its improvement. INTRODUCTION: This consensus article reviews the therapeutic strategies and management options for the treatment of osteoporosis of the oldest old. This vulnerable segment (persons over 80 years of age) stands to gain substantially from effective anti-osteoporosis treatment, but the under-prescription of these treatments is frequent. METHODS: This report is the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores some of the reasons for this and presents the arguments to counter these beliefs. The risk assessment of older individuals is briefly reviewed along with the differences between some intervention guidelines. The current evidence on the impact of nutritional deficiencies (i.e. calcium, protein and vitamin D) is presented, as are strategies to prevent falls. One possible reason for the under-prescription of pharmacological treatments for osteoporosis in the oldest old is the perception that anti-fracture efficacy requires long-term treatment. However, a review of the data shows convincing anti-fracture efficacy already by 12 months. RESULTS: The safety profiles of these pharmacological agents are generally satisfactory in this patient segment provided a few precautions are followed. CONCLUSION: These patients should be considered for particular consultation/follow-up procedures in the effort to convince on the benefits of treatment and to allay fears of adverse drug reactions, since poor adherence is a major problem for the success of a strategy for osteoporosis and limits cost-effectiveness.

The effect of maternal vitamin D concentration on fetal bone.

CONTEXT: Vitamin D deficiency during pregnancy may be associated with suboptimal fetal growth, but direct evidence is lacking. OBJECTIVES: The aim of the study was to validate a method for fetal femur volume (FV) measurement using three-dimensional ultrasound and to detect correlations between FV and maternal vitamin D concentration. DESIGN, SETTING, AND PARTICIPANTS: A novel method for assessing FV consists of three ultrasound measurements-femur length, proximal metaphyseal diameter (PMD), and midshaft diameter-and a volume equation; this was validated by comparing ultrasound to computed tomography measurements in six pregnancies after mid-trimester termination. This method was then applied in a cohort of healthy pregnant women participating in the Southampton Women Survey. Fetal three-dimensional ultrasound and maternal 25-hydroxyvitamin D [25(OH)D] levels were performed at 34 wk; dual-energy x-ray absorptiometry of the newborn was performed shortly after birth. Univariate and multiple linear regression analyses were performed between maternal characteristics and fetal outcomes. MAIN OUTCOME MEASURES: We performed ultrasound measurements of the fetal femur. RESULTS: In 357 pregnant participants, serum 25(OH)D correlated significantly with FV (P = 0.006; r = 0.147) and PMD (P = 0.001; r = 0.176); FV also demonstrated positive univariate correlations with maternal height (P < 0.001; r = 0.246), weight (P = 0.003; r = 0.160), triceps skinfold thickness (P = 0.013; r = 0.134), and a borderline negative effect from smoking (P = 0.061). On multiple regression, independent predictors of FV were the maternal height and triceps skinfold thickness; the effect of 25(OH)D on FV was attenuated, but it remained significant for PMD. CONCLUSION: Using a novel method for assessing FV, independent predictors of femoral size were maternal height, adiposity, and serum vitamin D. Future trials should establish whether pregnancy supplementation with vitamin D is beneficial for the fetal skeleton, using FV and PMD as fetal outcome measures.

Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study.

BACKGROUND: Vitamin D insufficiency is common in women of childbearing age and increasing evidence suggests that the risk of osteoporotic fracture in adulthood could be determined partly by environmental factors during intrauterine and early postnatal life. We investigated the effect of maternal vitamin D status during pregnancy on childhood skeletal growth. METHODS: In a longitudinal study, we studied 198 children born in 1991-92 in a hospital in Southampton, UK; the body build, nutrition, and vitamin D status of their mothers had been characterised during pregnancy. The children were followed up at age 9 years to relate these maternal characteristics to their body size and bone mass. FINDINGS: 49 (31%) mothers had insufficient and 28 (18%) had deficient circulating concentrations of 25(OH)-vitamin D during late pregnancy. Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body (r=0.21, p=0.0088) and lumbar-spine (r=0.17, p=0.03) bone-mineral content in children at age 9 years. Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p<0.0001 and p=0.0110, respectively) and childhood bone mass (p=0.0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p=0.0286). INTERPRETATION: Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium. Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.

Maternal and seasonal predictors of change in calcaneal quantitative ultrasound during pregnancy.

BACKGROUND: During pregnancy, mineralization of the fetal skeleton and obligate urinary losses require adaptation of maternal calcium homeostasis, such as increased intestinal calcium absorption and bone resorption. However, the environmental determinants of maternal bone resorption during pregnancy in healthy adult mothers have not been previously described. SUBJECTS AND METHODS: We conducted a population-based longitudinal study of 307 term pregnancies using a cohort of 307 pregnant women living in Southampton, United Kingdom. During early and late pregnancy, skeletal status was measured at the left calcaneus using quantitative ultrasound (QUS). RESULTS: There was a significant (P < 0.001) decline in both speed of sound and broadband ultrasound attenuation during pregnancy. Those women who were pregnant for the first time (P = 0.001), had low milk intake prepregnancy (P = 0.01), and reduced measures of fat mass (P = 0.01) showed the greatest decline in calcaneal bone measurements. Furthermore, those women who were pregnant over winter months had greater losses in calcaneal QUS (P = 0.02). CONCLUSION: Maternal lifestyle, fat stores, and seasonality of early pregnancy influence maternal calcaneal QUS loss during pregnancy; the findings support a role for vitamin D supplementation of women pregnant during winter, especially those with low calcium intakes who are pregnant for the first time.