[Physical therapy in rheumatology : What, when and how can it be prescribed?] / Physikalische Therapie in der Rheumatologie : Was, wann und wie kann man es verschreiben?

Treatment of a rheumatic diseases without physical and occupational therapy is almost incomplete because it cannot be replaced by anything else; however, slightly less than half of all insured persons with inflammatory rheumatic diseases only receive an outpatient prescription and this proportion has hardly changed in the last 15 years. This is even more surprising as those affected persons often have limitations in functional health due to multimorbidity, which are very accessible by physical measures. The article is intended to serve as a basis for a recourse-proof prescription in order to make even greater use of the corresponding possibilities of an outpatient physical prescription in the future.

[Cognitive training and physical therapy for fibromyalgia : Results of the KogTraP pilot study]. / Kognitives Training und physikalische Therapie bei Fibromyalgie : Ergebnisse der KogTraP-Pilotstudie.

BACKGROUND: The effectiveness of additive cognitive training in groups to the standard physical-medical therapy for primary and secondary fibromyalgia syndrome (p/sFMS) and a subsequent home-based self-training phase (STP) was analyzed. METHODS: In the prospective controlled randomized study, 32 people with confirmed p/sFMS were included, whereby 4 patients could not be evaluated. During 2 weeks of acute inpatient therapy, the control group (CG; n = 12) received standard physical-medical therapy and the intervention group (IG, n = 16) also received social-communicative cognitive group training (once/day, 60 min). In the subsequent 3­months, STP training was continued by both groups. RESULTS: Outcome parameters at baseline (U1), at discharge (U2), and after a quarter year (U3) were pain, well-being/depressive mood, general health, and cognitive parameters (memory functions, cognitive speed). Both groups showed significant pain relief (U2 vs. U1), which was 10% more in the IG. A significant improvement in mood could be seen in both groups, but only the IG no longer achieved depressive values in the follow-up (U3). An improvement in the general state of health was also detected in both groups, which was only maintained in the IG until the end of the STP. Cognitive performance remained the same in the IG at U2, while there was a reduction in the CG; cognitive speed could only be further improved in the IG during the STP. Adding cognitive training to a standard physical-medical clinical therapy resulted in significant pain relief and improvement of depression in patients during a hospital stay.

[Physical medicine for coincidence of cancer and inflammatory rheumatic disease : What speaks in favour and what to consider?] / Physikalische Medizin bei Koinzidenz einer Krebserkrankung und entzündlich-rheumatischen Erkrankung : Was spricht dafür und worauf ist zu achten?

The coincidence of an inflammatory rheumatic and a malignant disease causes a physical, cognitive and psychological reduction in performance. The prescription of physical therapy is therefore essential to address safety issues associated with both diseases, as well as side effects associated with antirheumatic and antineoplastic therapy that can impact the treatment. It is important to perform a risk assessment prior to physical therapy to identify potential safety issues and to determine baseline physical and functional status. In this review article descriptive information and the current literature on the safety of physical therapy interventions for people with rheumatic and malignant disease are highlighted, taking the disease process, treatment side effects and associated precautions and contraindications into account.

Therapeutic strategies in preclinical stages of rheumatoid arthritis.

Modern therapies and treatment algorithms, such as the treat­to­target strategy, have significantly improved outcomes in patients with rheumatoid arthritis (RA) over the past decades. Moreover, the concept of the "window of opportunity" has led to earlier diagnosis and better treatment outcomes. Nevertheless, progressive disease remains a significant clinical issue and socioeconomic burden, which warrants investigation of novel strategies. One of such innovative therapies is primary prevention: treating patients at risk for developing RA for a short period of time to prevent the disease before it occurs. The initiation of treatment in preclinical phases of RA is expected to delay, halt, or even prevent the disease onset or progression in the long term. This review summarizes this new concept, discusses current studies including an overview of therapeutic algorithms and findings, and provides a critical evaluation of pharmacologic approach in the preclinical stages of RA.

Prevalence and effects of Vitamin D receptor polymorphism on bone mineral density and metabolism in patients with systemic sclerosis: a preliminary study.

Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR) gene have been associated with osteoporosis in patients with autoimmune diseases. The aim of this study was to investigate the prevalence and possible effects of VDR polymorphism on BMD and bone metabolism in patients with SSc. In patients with SSc measurement of BMD was performed using dual-energy X-ray absorptiometry. VDR polymorphisms (FokI, BsmI) were genotyped using restriction fragment length polymorphism analysis. Markers of bone metabolism (calcium, osteocalcin, ß-crosslaps) were determined. Primary endpoint was the prevalence of VDR gene polymorphisms and the association with reduced BMD. Secondary endpoints included associations between bone metabolism and VDR gene polymorphism. 79 Caucasian patients with SSc were included. Overall, 83.5% had reduced BMD (51.9% osteopenia, 31.6% osteoporosis). The prevalence of VDR gene polymorphism (73% BsmI, 77% FokI) was comparable to studies in healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. Fokl polymorphism was significantly associated with reduced CTX levels, although changes remained within the reference limits. VDR polymorphisms can frequently be found in patients with SSc in comparable prevalence to healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. This could be a possible contributor for the high prevalence of reduced BMD in 83.5% of patients with SSc in this study.Trial registration. DRKS00032768, date: 05.10.2023, retrospectively registered.

[Update on the DVO Guideline 2023 "Prophylaxis, diagnosis and treatment of osteoporosis in postmenopausal women and in men aged over 50"-What's new for rheumatology?] / Update DVO-Leitlinie 2023 "Prophylaxe, Diagnostik und Therapie der Osteoporose bei postmenopausalen Frauen und bei Männern ab dem 50. Lebensjahr" ­ Was ist neu für die Rheumatologie?

In October 2023, the organization of the German-speaking scientific osteological societies (DVO) published the revised guideline on the "Prophylaxis, diagnosis and treatment of osteoporosis in postmenopausal women and in men aged over 50." This review article reflects the new features of the guideline and their relevance in the care of patients with inflammatory rheumatic diseases.A key innovation is the change from the 10-year fracture risk to the 3­year fracture risk. Basic diagnostics are currently performed without a defined fracture threshold. Treatment thresholds for specific osteological therapy constitute another key innovation, defined as 3% to < 5%, 5% to < 10%, and from 10% for vertebral body and femoral neck fractures. If the 3­year fracture risk is > 10%, osteoanabolic therapy should primarily be carried out and antiresorptive therapy is initiated following osteoanabolic therapy. In addition, patients with osteoporosis and prolonged glucocorticoid therapy should primarily be treated osteoanabolically with teriparatide. In summary, the changes to the DVO guideline reflect the latest scientific study findings in osteology and lead to detailed differential therapy for osteoporosis.

Heat therapy in rheumatic and musculoskeletal diseases - an overview of clinical and molecular effects.

Rheumatic and musculoskeletal diseases (RMDs) usually lead to morphological and functional deficits of various extend, increased morbidity and a considerable loss of quality of life. Modern pharmacological treatment has become effective and can stop disease progression. Nonetheless, disease progression is often only slowed down. Moreover, pharmacological treatment does not improve functionality per se. Therefore, multimodal treatment of rheumatic disorders with physical therapy being a key element is of central importance for best outcomes. In recent years, research into physical medicine shifted from a sole investigation of its clinical effects to a combined investigation of clinical effects and potential changes in the molecular level (e.g., inflammatory cytokines and the cellular autoimmune system), thus offering new explanations of clinical effects of physical therapy. In this review we provide an overview of studies investigating different heat applications in RMDs, their effect on disease activity, pain and their influence on the molecular level.

Enhancing student understanding of rheumatic disease pathologies through augmented reality: findings from a multicentre trial.

OBJECTIVE: The possibility of combining real and virtual environments is driving the increased use of augmented reality (AR) in education, including medical training. The aim of this multicentre study was to evaluate the students' perspective on the AR-based Rheumality GO!® app as a new teaching concept, presenting six real anonymised patient cases with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). METHODS: The study encompassed 347 undergraduate medical students (232 women and 115 men) from four medical universities in Germany (Jena, Bad Nauheim/Gießen, Nuremberg, Erlangen). The course was divided into a theoretical refresher lecture followed by six AR-based cases in each of the three indications presented in the Rheumality GO!® app. All participants evaluated the course after completion, assessing the benefit of the app from a student´s perspective using a questionnaire with 16 questions covering six subject areas. RESULTS: The use of the AR-based app Rheumality GO!® improved the understanding of pathologies in RA, PsA, and axSpA for 99% of the participants. For 98% of respondents, the concept of AR with real patient data has made a positive impact on the teaching environment. On the other hand, 82% were in favour of the use of virtual tools (e.g. AR) in addition to this conventional approach. CONCLUSION: The results of our survey showed that from medical students' perspective, an AR-based concept like the Rheumality GO!® app can complement rheumatology teaching in medical school as an effective and attractive tool though not replace bedside teaching.

Additive Effects of Exercise and Vitamin D Supplementation (with and without Calcium) on Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis.

Exercise is a recognized component in the prevention and therapy of osteoporosis. The present systematic review and meta-analysis aimed to determine the effect of Vitamin D (Vit-D) added to exercise versus exercise alone on bone mineral density (BMD) at the lumbar spine (LS) or hip in older adults. A systematic review based on six literature databases according to PRISMA included (a) exercise trials, with an exercise (EX) and a combined exercise + Vit-D group (EX + Vit-D), (b) intervention ≥ 6 months, and (c) BMD assessments at LS or hip. Effects sizes (MD) and 95%-confidence intervals (95%-CI) were calculated using a random-effect model that includes the inverse heterogeneity model (IVhet). Five studies with 281 participants in the EX and 279 participants in the EX + Vit-D were included. No significant differences between EX versus EX + Vit-D were observed for BMD-LS (MD: 0.002, 95%-CI: -0.033 to 0.036) or BMD-hip (MD: 0.003, 95%-CI: -0.035 to 0.042). Heterogeneity between the trial results was moderate-substantial for LS (I2 = 0%) and moderate for hip-BMD (I2 = 35%). The funnel plot analysis suggests evidence for a publication/small study bias for BMD-LS and hip results. In summary, this present systematic review and meta-analysis were unable to determine significant positive interaction of exercise and Vit-D on LS- or hip-BMD. We predominately attribute this finding to (1) the less bone-specific exercise protocols of at least two of the five studies and (2) the inclusion criteria of the studies that did not consequently focus on Vit-D deficiency. This issue should be addressed in more detail by adequately powered exercise trials with promising exercise protocols and participants with Vit-D deficiency. This trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42022309813.

Global Functioning in Axial Spondyloarthritis is Stronger Associated With Disease Activity and Function Than With Mobility and Radiographic Damage.

OBJECTIVE: The Assessment of Spondyloarthritis International Society Health Index (ASAS HI) is a validated patient-reported outcome (PRO) for global functioning of patients with axial spondyloarthritis (axSpA). The Epionics SPINE (ES) is an electronic device for assessment of axial mobility that provides an objective measure of spinal mobility by assessing range of motion (RoM) and range of kinematics (RoK). The aim of this study is to investigate the relationship between global functioning and clinical measures of disease activity, physical function, spinal mobility, and radiographic damage. METHODS: In a cross-sectional study design, consecutive patients with radiographic and nonradiographic axSpA were included, and the following established tools were assessed: Bath ankylosing spondylitis (AS) disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI), ASAS HI, and RoM and RoK using ES. Structural damage of spine and sacroiliac joints (SIJ) were assessed by counting the number of syndesmophytes and by New York grading of sacroiliitis. Kendall's tau correlation coefficients were calculated. RESULTS: In 103 patients with axSpA, ASAS HI scores correlated significantly with PRO scores (BASDAI, r = 0.36; BASFI, r = 0.48; and back pain, r = 0.41; all P < 0.001). In contrast, no significant correlation between ASAS HI and RoM and RoK (r between -0.08 and 0.09) and radiographic damage in SIJ and spine (all r between 0.03 and 0.004) were seen, respectively. BASMI scores correlated weakly (r = 0.14; P = 0.05). CONCLUSION: This study shows that axSpA disease-specific PROs have an impact on global functioning, whereas spinal mobility scores, even if objectively assessed by the ES, have limited impact on patient reported-global functioning. The results also suggest that global functioning is, in this cohort, not much dependent on the degree of structural damage in the axial skeleton.

[Lifestyle medication vitamin D. What evidence is available?] / Lifestyle-Medikament Vitamin D. Was gibt es an Evidenz?

An undersupply of 25-(OH) vitamin D3 (calcifediol) exists in many countries with moderate sunlight, long winters and only moderate fish consumption. Risk groups for vitamin D3 deficiency are older persons over 65 years, geriatric persons in nursing homes, infants and children/adolescents. Therefore, there are also many situations in Germany which justify vitamin D substitution; however, vitamin D3 is currently praised as a "magic bullet" against everything. But what do the data look like? Where can it help and where can it not help?

Clinical Relevance of Axial Radiographic Damage in Axial Spondyloarthritis: Evaluation of Functional Consequences by an Objective Electronic Device.

OBJECTIVE: Axial spondyloarthritis (axSpA) is associated with decreased function and mobility of patients as a result of inflammation and radiographic damage. The Epionics SPINE device (ES), an electronic device that objectively measures spinal mobility, including range of motion (RoM) and speed (ie, range of kinematics [RoK]) of movement, has been clinically validated in axSpA. We investigated the performance of the ES relative to radiographic damage in the axial skeleton of patients with axSpA. METHODS: A total of 103 patients with axSpA, 31 with nonradiographic axSpA (nr-axSpA) and 72 with radiographic axSpA (r-axSpA), were consecutively examined. Conventional radiographs of the spine (including presence, number, and location of syndesmophytes) and the sacroiliac joints (SIJs; rated by the modified New York criteria) were analyzed with the ES. Function and mobility were assessed using analyses of covariance and Spearman correlation. RESULTS: The number of syndesmophytes correlated positively with Bath Ankylosing Spondylitis Metrology Index scores (r 0.38, P = 0.02) and correlated negatively with chest expansion (r -0.39, P = 0.02) and ES measurements (-0.53 ≤ r ≤ -0.34, all P < 0.03), except for RoM and RoK regarding rotation and RoK for extension of the lumbar and thoracic spines. In the radiographic evaluation of the SIJs, the extent of damage correlated negatively with ES scores and metric measurements (-0.49 ≤ r ≤ -0.33, all P < 0.001). Patients with r-axSpA, as compared to those with nr-axSpA, showed significantly worse ES scores for RoM, RoK, and chest expansion. CONCLUSION: The ES scores, in accordance with mobility measurements, correlated well with the presence and extent of radiographic damage in the spine and the SIJs. As expected, patients with r-axSpA had more severe impairments than those with nr-axSpA.

Camurati-Engelmann Disease: A Case-Based Review About an Ultrarare Bone Dysplasia.

Camurati-Engelmann disease or progressive diaphyseal dysplasia is a rare hereditary disease that results in a symmetrical hyperostosis of the long bones (cortical thickening) and/or the base of the skull. Camurati-Engelmann disease is also associated with myopathy and neurological manifestations. Clinically, Camurati-Engelmann disease typically presents with bone pain in the lower extremities, muscle weakness, and a wobbly, stilted gait. The disease is caused by mutations in the transforming growth factor-beta 1 gene. Up to date, about 300 cases have been described in the literature. In this case-based review, we present the clinical picture and genetic and radiological findings in a 20-yearold male patient we diagnosed with Camurati-Engelmann disease and our considerations in his treatment and compare the case to the literature. The diagnosis of Camurati-Engelmann disease was confirmed on patients' history, clinical and radiological findings, and genetic testing for transforming growth factor beta-1 mutation. The patient responded well to single therapy with zoledronic acid. Early diagnosis leads to improved clinical outcomes and increased quality of life in affected patients.

The effect of aquatic exercise on bone mineral density in older adults. A systematic review and meta-analysis.

Introduction: Aquatic or water-based exercise is a very popular type of exercise in particular for people with physical limitations, joint problems and fear of falling. The present systematic review and meta-analysis aimed to provide evidence for the effect of aquatic exercise on Bone Mineral Density (BMD) in adults. Methods: A systematic literature search of five electronic databases (PubMed/MEDLINE, Cochrane Library, Scopus, Web of Science and CINAHL) according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was conducted until 2022/01/30, with an update to 2022/10/07. We included controlled trials with a duration of more than 6 months and at least two study groups, aquatic exercise (EG) versus non-training controls (CG) with no language restrictions. Outcome measures were standardized mean differences (SMD) with 95%-confidence intervals (95%-CI) for BMD changes at the lumbar spine (LS) and femoral neck (FN). We applied a random-effects meta-analysis and used the inverse heterogeneity (IVhet) model to analyze the data. Results: Excluding an outlier study with an exceptionally high effect size for LS-BMD, we observed a statistically significant (p = .002) effect (EG vs. CG) of aquatic exercise for the LS-BMD (n = 10; SMD: 0.30; 95%-CI: 0.11-0.49). In parallel, the effect of aquatic exercise on FN-BMD was statistically significant (p = .034) compared to the CG (n = 10; SMD: 0.76, 95%-CI: 0.06-1.46). Of importance, heterogeneity between the trial results was negligible for LS (I2: 7%) but substantial for FN-BMD (I2: 87%). Evidence for risks of small study/publication bias was low for LS-BMD and considerable for FN-BMD. Discussion: In summary, the present systematic review and meta-analysis provides further evidence for the favorable effect of exercise on bone health in adults. Due to its safety and attractiveness, we particularly recommend water-based exercise for people unable, afraid or unmotivated to conduct intense land-based exercise programs.

Exercise effects on glucocorticoid-induced bone loss in adults: a systematic review and meta-analysis.

Objectives: Due to their pronounced anti-inflammatory and immunosuppressive effects, glucocorticoids (GCs) are widely used in inflammatory conditions and organ transplants. Unfortunately, GC-induced osteoporosis is one of the most common causes of secondary osteoporosis. The aim of the present systematic review and meta-analysis was to determine the effect of exercise added to GC therapy on BMD at the lumbar spine or femoral neck in people on GC therapy. Methods: A systematic literature search of five electronic databases included controlled trials with a duration of >6 months and at least two study arms [glucocorticoids (GCs) and GCs and exercise (GC + EX)] were conducted up to 20 September 2022. Studies involving other pharmaceutical therapies with relevant effects on bone metabolism were excluded. We applied the inverse heterogeneity model. Outcome measures were standardized mean differences (SMDs) with 95% CIs for BMD changes at the lumbar spine (LS) and femoral neck (FN). Results: We identified three eligible trials with a total of 62 participants. In summary, the GC + EX intervention indicated statistically significantly higher SMDs for LS-BMD [SMD 1.50 (95% CI 0.23, 2.77)] but not for FN-BMD [0.64 (95% CI -0.89, 2.17)] compared with GC treatment alone. We observed substantial heterogeneity (LS-BMD I 2 = 71%, FN-BMD I 2 = 78%) between the study results. Conclusion: Although more well-designed exercise studies are needed to address the issue of exercise effects on GC-induced osteoporosis (GIOP) in more detail, upcoming guidelines should pay more attention to the aspect of exercise for bone strengthening in GIOP. Registration number: PROSPERO: CRD42022308155.

Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators.

The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I2 = 20%, TH BMD) to substantial (I2 = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur.

Exercise and the prevention of major osteoporotic fractures in adults: a systematic review and meta-analysis with special emphasis on intensity progression and study duration.

The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized exercise protocols are very rare. In the present work, we provided positive evidence for exercise effects on the number of osteoporotic fractures in adults, albeit without observing any significant relevance of intensity progression or study duration. INTRODUCTION: Osteoporotic fractures are a major challenge confronting our aging society. Exercise might be an efficient agent for reducing osteoporotic fractures in older adults, but the most promising exercise protocol for that purpose has yet to be identified. The present meta-analysis thus aimed to identify important predictors of the exercise effect on osteoporotic fractures in adults. METHODS: We conducted a systematic search of six literature databases according to the PRISMA guideline that included controlled exercise studies and reported the number of low-trauma major osteoporotic fractures separately for exercise (EG) and control (CG) groups. Primary study outcome was incidence ratio (IR) for major osteoporotic fractures. Sub-analyses were conducted for progression of intensity (yes vs. no) during the trial and the study duration (≤ 12 months vs. > 12 months). RESULTS: In summary, 11 studies with a pooled number of 9715 participant-years in the EG and 9592 in the CG were included. The mixed-effects conditional Poisson regression revealed positive exercise effects on major osteoporotic fractures (RR: 0.75, 95% CI: 0.54-0.94, p = .006). Although studies with intensity progression were more favorable, our subgroup analysis did not determine significant differences for diverging intensity progression (p = .133) or study duration (p = .883). Heterogeneity among the trials of the subgroups (I2 ≤ 0-7.1%) was negligible. CONCLUSION: The present systematic review and meta-analysis provided significant evidence for the favorable effect of exercise on major osteoporotic fractures. However, diverging study and exercise characteristics along with the close interaction of exercise parameters prevented the derivation of reliable recommendations for exercise protocols for fracture reductions. PROSPERO ID: CRD42021250467.

Exercise Reduces the Number of Overall and Major Osteoporotic Fractures in Adults. Does Supervision Make a Difference? Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis (PROSPERO ID: CRD42021250467) was to evaluate the effects of exercise on low-trauma overall and major osteoporotic fractures (hip, spine, forearm, or humerus fractures) and to determine the corresponding effect of supervision of the exercise program. Our systematic search of six literature databases according to the PRISMA guideline was conducted from January 1, 2013 (ie, date of our last search) to May 22, 2021, and included controlled clinical exercise trials with (i) individuals aged ≥45 years, (ii) cohorts without therapies/diseases related to fractures, (iii) observation periods of ≥3 months, and (iv) the number of low-trauma fractures listed separately for the exercise (EG) and control (CG) groups. We included 20 intervention studies with 21 EGs and 20 CGs comprising a pooled number of participant-years of n = 11.836 in the EG and n = 11.275 in the CG. The mixed-effects conditional Poisson regression revealed significant effects of exercise on low-trauma overall incidence (rate) ratio (IR 0.67, 95% confidence interval [95% CI] 0.51-0.87) and major osteoporotic fractures IR (0.69, 95% CI 0.52-0.92). Heterogeneity between the trials was moderate for low-trauma overall (I2 = 40%) and negligible (I2 < 1%) for major osteoporotic fractures. Supervision of the exercise program plays a significant role in the reductions of overall and major osteoporotic fractures with IR about twice as favorable in the predominately supervised (IR 0.44; 95% CI 0.27-0.73 and 0.38; 0.19-0.76) versus the predominately non-supervised exercise trials (IR 0.83; 95% CI 0.60-1.14 and 0.82; 0.64-1.05). In summary, the present study provides evidence for the positive effect of exercise on low-trauma overall and major osteoporotic fractures in middle aged to older adults. Supervision of the exercise program is a crucial aspect in exercise programs on fracture reduction. Thus, home-based exercise protocols should increasingly implement online classes to ensure widely consistent supervision and monitoring of the exercise program. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).