Does adding exercise or physical activity to pharmacological osteoporosis therapy in patients with increased fracture risk improve bone mineral density and lower fracture risk? A systematic review and meta-analysis.

This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [- 1.71; 2.06], n = 3 studies), tibia (0.25 [- 4.85; 5.34], n = 2), lumbar spine (0.20 [- 1.15; 1.55], n = 4), and forearm (0.05 [- 0.35; 0.46], n = 3), but not femoral neck (- 0.03 [- 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (- 0.68 [- 5.88; 4.53], n = 3), PINP (- 0.74 [- 10.42; 8.93], n = 2), and CTX-I (- 0.69 [- 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. PROTOCOL REGISTRATION: PROSPERO CRD42022336132.

Effects of non-pharmacological interventions on sleep in chronic low back pain: A systematic review and meta-analysis of randomised controlled trials.

Low back pain is a leading cause of disability worldwide and adults with chronic low back pain (≥12weeks) commonly experience sleep impairments (e.g., insomnia, sleep disturbance). This study examined the effects of non-pharmacological interventions on sleep in adults with chronic low back pain. Six databases (PubMed, CINAHL, SPORTDiscus, PsycINFO, EMBASE, CENTRAL) were searched from inception to 2 June 2021 for randomised controlled trials. Pairwise random-effect meta-analysis estimated standardised mean difference (Hedges' g) at end-of-intervention follow-up. Nineteen studies (participants: 1348) were included. When compared to control, non-pharmacological interventions improved sleep (g [95%CI]: -0.33 [-0.56, -0.11], p = 0.004, small effect, I2 = 59.3%; n = 879; studies: n = 13; GRADE: low). This small improvement in sleep was associated with a moderate reduction in pain intensity (-0.69 [-1.00, -0.38], p < 0.001, I2 = 75.3%; n = 812; studies: n = 12; GRADE: very low) and no changes in back-related disability (-0.50 [-1.13, 0.14], p = 0.129, I2 = 91.4%; n = 517; studies: n = 6; GRADE: low). Notably, all eligible studies reported interventions primarily aimed to reduce pain, although our search criteria were not limited to pain interventions. Key limitations were data paucity and high risk of bias. Future research should investigate sleep-based interventions (i.e., those purposely designed to improve sleep) using subjective and objective measures across a range of sleep domains (CRD42021275227).

Assessing safety and treatment efficacy of running on intervertebral discs (ASTEROID) in adults with chronic low back pain: protocol for a randomised controlled trial.

Poor intervertebral disc (IVD) health is associated with low back pain (LBP). This 12-week parallel randomised controlled trial will evaluate the efficacy of a progressive interval running programme on IVD health and other clinical outcomes in adults with chronic LBP. Participants will be randomised to either a digitally delivered progressive interval running programme or waitlist control. Participants randomised to the running programme will receive three individually tailored 30 min community-based sessions per week over 12 weeks. The waitlist control will undergo no formal intervention. All participants will be assessed at baseline, 6 and 12 weeks. Primary outcomes are IVD health (lumbar IVD T2 via MRI), average LBP intensity over the prior week (100-point visual analogue scale) and disability (Oswestry Disability Index). Secondary outcomes include a range of clinical measures. All outcomes will be analysed using linear mixed models. This study has received ethical approval from the Deakin University Human Research Ethics Committee (ID: 2022-162). All participants will provide informed written consent before participation. Regardless of the results, the findings of this study will be disseminated, and anonymised data will be shared via an online repository. This will be the first study to evaluate whether a progressive interval running programme can improve IVD health in adults with chronic LBP. Identifying conservative options to improve IVD health in this susceptible population group has the potential to markedly reduce the burden of disease. This study was registered via the Australian New Zealand Clinical Trials Registry on 29 September 2022 (ACTRN12622001276741).

Effects of pharmacotherapy on sleep-related outcomes in adults with chronic low back pain: A systematic review and meta-analysis of randomised controlled trials.

Background: Adults with chronic low back pain (CLBP) suffer impaired sleep. Medications for CLBP can impact sleep which in turn may influence treatment outcomes. This systematic review and meta-analysis examined the effects of pharmacotherapy (any type) on sleep in adults with CLBP. Methods: In this systematic review and meta-analysis, we searched PubMed, CINAHL, SPORTDiscus, PsycINFO, EMBASE, and CENTRAL from inception to 10 July 2022. Randomised controlled trials that investigated the effects of pharmacotherapy on sleep in adults with CLBP were included. Manual citation search of relevant systematic reviews and included studies were also conducted. Mean change from baseline for sleep outcomes (e.g., sleep quality, total sleep time, wake after sleep onset) was the effect of interest. Pairwise inverse-variance random effect meta-analysis was performed to impute pooled estimates (Hedges' g or risk ratios). The Hartung-Knapp-Sidik-Jonkman method was used where there were ≤5 studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used for evaluating the certainty of evidence. This study was registered with PROSPERO (CRD42022309419). Findings: Assessment of 3959 records resulted in nine studies (n = 2927) being included. Pharmacotherapy for CLBP management had a small, yet unlikely clinically significant, effect on improving sleep in adults with CLBP, when compared to placebo (g [95% CI]: -0.23 [-0.37, -0.09], p = .0009; I 2  = 30.1%; n = 1433; studies: n = 8; GRADE: low). Notably, no eligible studies investigated the effect of sleep medications in this population, despite being within the scope of this review. Interpretation: Pharmacotherapy used to manage CLBP provided improvements in sleep in adults with CLBP. Given that these effects were small and unlikely clinically significant, clinicians could consider alternative treatments (e.g., non-pharmacological interventions) for managing sleep in adults with CLBP. However, low to very low certainty of evidence precluded strong conclusions. To improve certainty of evidence and confidence in the effect estimates, future research needs to use robust method to minimise bias. Additional research evaluating multiple sleep characteristics, using both validated objective and subjective measures, is also warranted to further investigate the influence of distinct sleep parameters. Funding: The Summer Research Scholarship from the Appleton Institute, Central Queensland University, Australia.

Interventions to improve sleep in caregivers: A systematic review and meta-analysis.

Unpaid caregivers often experience sleep impairments as an unintended consequence of providing care. This systematic review and meta-analysis investigated the efficacy of interventions to improve sleep in unpaid caregivers. Six databases were searched from journal inception to 7-Sep-2021 to identify randomised controlled trials. Random-effects meta-analyses estimated mean differences (MD) at end-of-intervention. Twenty-one studies were identified (15 eligible for meta-analysis). Compared to control, interventions improved sleep quality (Pittsburgh Sleep Quality Index; 12 studies, 1153 participants, MD = -1.66, 95% CI [-2.91, -0.41], p = 0.009, I2 = 90.51%, GRADE = low), and total sleep time (hours; two studies, 122 participants, MD = 0.45, 95% CI [0.42, 0.48], p = 0.003, I2 = 0.00%, GRADE = low), but not sleeping problems (sleep item on Symptom Distress Scale of the Omega Screening Questionnaire; two studies, 529 participants, MD = -0.06, 95% CI [-0.69, 0.58], p = 0.458, I2 = 0.01%, GRADE = low). There is low quality evidence that interventions improve sleep quality in unpaid caregivers compared to control. Limitations include the lack of evidence for specific intervention modes and limited use of objective sleep measures. Future research should explore potential effect modifiers such as care recipient condition (CRD42021278670).