Comparing medication adherence in patients receiving bisphosphonates for preventing fragility fractures: a comprehensive systematic review and network meta-analysis

Background: Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits. Objective: To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate). Methods: Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients’ adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users’ likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method. Results: Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data. Conclusions: Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates’ users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates. Trial registration: PROSPERO 2020 CRD42020177166

Enclosing a pen reduced time to response to questionnaire mailings

OBJECTIVES: To assess the effectiveness of including a pen in postal questionnaires on response rate, necessity of reminders, time to response, and completeness of response to the primary outcome question (POQ).   STUDY DESIGN AND SETTING: A two-arm randomized controlled trial (RCT) embedded within the screening of older women for prevention of fracture trial (SCOOP). Women, aged 70-75 years, were randomized to receive a pen with their questionnaire (n = 3,826) or to receive the questionnaire alone (n = 3,829). The results were combined with another embedded RCT in a meta-analysis.   RESULTS: A response rate of 92.4% was observed in the pen group compared with 91.3% in the control group (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 0.98, 1.37; P = 0.08). There was a difference in reminders required (OR = 0.88; 95% CI: 0.79, 0.98; P = 0.02), time to response (hazard ratio = 1.06; 95% CI: 1.01, 1.11; P = 0.01) and some difference in the completeness of response to the POQ (OR = 1.18; 95% CI: 1.00, 1.39; P = 0.05). The pooled OR from the meta-analysis for response rate was 1.21 (95% CI: 1.05, 1.39; P = 0.01).   CONCLUSION: Inclusion of a pen with postal questionnaires potentially has a positive impact on response rates and the number of reminders required. There may be some reduction in time to response. Studies of different participant groups are needed to test the effectiveness over more diverse populations

UK clinical guideline for the prevention and treatment of osteoporosis

The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management. INTRODUCTION The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. METHODS Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence. RESULTS Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement. CONCLUSION The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases

25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression

Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), but not inactive 25-hydroxyvitamin D3 (25OHD3), correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02), velocity (Vmax, rho = 0.40, p = 0.02) and jump height (rho = 0.36, p = 0.04). Lean mass correlated positively with 1α,25(OH)2D3 (rho = 0.47, p = 0.02), in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively). Serum 25OHD3 and 24,25(OH)2D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR) mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH)2D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH)2D3 has limited effects on muscle gene expression, but is associated with increased muscle strength and lean mass in women. These pleiotropic effects of the vitamin D ‘metabolome’ on muscle function indicate that future supplementation studies should not be restricted to conventional analysis of the major circulating form of vitamin D, 25OHD3

A Retrospective Cohort Study Evaluating the Prevalence of Vitamin D Deficiency and its Impact on the Biochemical and Clinical Presentations of Patients with Primary Hyperparathyroidism (PHPT)

Abstract Background: Primary Hyperparathyroidism (PHPT) is the third most common endocrine disorder, with an estimated prevalence of 1 to 4 per 1,000 in the general population. It is well established that vitamin D deficiency co-exists with PHPT. However, there are very few studies that have compared the prevalence of vitamin D deficiency between symptomatic and asymptomatic PHPT patients. Aim: This research evaluated the prevalence of vitamin D deficiency in patients with PHPT, and compared the prevalence of vitamin D deficiency in patients with symptomatic and asymptomatic disease. Methods: This observational cohort study employed a retrospective design where clinical records of 400 new patients referred to the metabolic bone clinics for investigation of hypercalcaemia, between 2010 and 2017, were reviewed. The study population was grouped as ‘asymptomatic’ or ‘symptomatic’ based on the absence or presence of at least one classical hypercalcaemia-related symptom. Results: PHPT is more prevalent in women with female to male ratio of 4.4:1. Symptomatic patients were significantly younger compared to the asymptomatic group (60.97 year+15.356 vs 65.88 years+13.924, p=0.001). There was a high prevalence of vitamin D deficiency (64.25%) with no difference between the symptomatic and asymptomatic groups. The prevalence of osteoporosis was 53.35% whilst the prevalence of renal stone was 13.54% with no between group differences. Conclusion: PHPT is more common in women than in men. Symptomatic patients were younger compared with those without symptoms. Vitamin D deficiency is highly prevalent in patients with PHPT regardless of whether the patients were symptomatic or not

Review: New perspectives in the management of primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a biochemical syndrome caused by the inappropriate or unregulated overproduction of parathyroid hormone, leading to hypercalcaemia. It was previously considered a relatively rare disorder, with clinical manifestations dominated by renal and/or bone disease. However, in modern times the diagnosis is most frequently recognized coincidentally on biochemical testing in patients evaluated for unrelated complaints. Parathyroidectomy is the only curative treatment for PHPT, with improved outcomes in symptomatic patients following this procedure. However, surgical intervention in patients with no clear clinical features remains controversial. The National Institutes for Health (NIH) have developed consensus guidelines giving specific indications for when surgery is recommended in patients with asymptomatic PHPT. This article examines the impact of treatment on asymptomatic PHPT, focusing on bone disease, neurocognitive function, quality of life, cardiovascular disease and mortality. Medical treatment options, including bisphosphonates and cinacalcet, are also discussed