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JAMA Network Open May 2024Corticosteroid injections (CSIs) are an important tool for pain relief in many musculoskeletal conditions, but the longitudinal effects of these treatments on bone...
IMPORTANCE
Corticosteroid injections (CSIs) are an important tool for pain relief in many musculoskeletal conditions, but the longitudinal effects of these treatments on bone health and fracture risk are unknown.
OBJECTIVE
To determine whether cumulative doses of corticosteroid injections are associated with higher risk of subsequent osteoporotic and nonosteoporotic fractures.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included adult patients receiving any CSI from May 1, 2018, through July 1, 2022. Eligible patients resided in Olmsted County, Minnesota, and were empaneled to receive primary care within the Mayo Clinic. Cox proportional hazards regression models were used to evaluate risk of fracture based on cumulative injected corticosteroid dose.
EXPOSURE
Receipt of any CSI during the study period.
MAIN OUTCOMES AND MEASURES
The primary outcome was risk of fracture by total triamcinolone equivalents received. Secondary outcomes consisted of risks of fracture based on triamcinolone equivalents received in subgroups of patients not at high risk for fracture and patients with osteoporosis.
RESULTS
A total of 7197 patients were included in the study (mean [SD] age, 64.4 [14.6] years; 4435 [61.6%] women; 183 [2.5%] Black and 6667 [92.6%] White), and 346 (4.8%) had a new fracture during the study period. Of these fractures, 149 (43.1%) were considered osteoporotic. In the adjusted Cox proportional hazards regression model, there was no association of higher fracture risk based on cumulative CSI dose (adjusted hazard ratio [HR], 1.04 [95% CI, 0.96-1.11]). There was also no associated higher risk of fracture in the non-high-risk (adjusted HR, 1.11 [95% CI, 0.98-1.26]) or osteoporosis (adjusted HR, 1.01 [95% CI, 0.90-1.11]) subgroups. Age, Charleson Comorbidity Index, and previous fracture were the only factors that were associated with higher fracture risk.
CONCLUSIONS AND RELEVANCE
In this cohort study of cumulative injected corticosteroid dose and risk of subsequent fracture, no association was observed, including in patients with a preexisting diagnosis of osteoporosis. Treatment of painful conditions with CSI should not be withheld or delayed owing to concern about fracture risk.
Topics: Humans; Female; Male; Middle Aged; Aged; Adrenal Cortex Hormones; Fractures, Bone; Minnesota; Osteoporosis; Cohort Studies; Proportional Hazards Models; Risk Factors; Osteoporotic Fractures
PubMed: 38819820
DOI: 10.1001/jamanetworkopen.2024.14316 -
Osteoporosis International : a Journal... Jun 2024It remains unclear whether the association between metformin and osteoporosis (OP) risk is causal. This two-sample Mendelian randomization (MR) study suggests a causal...
UNLABELLED
It remains unclear whether the association between metformin and osteoporosis (OP) risk is causal. This two-sample Mendelian randomization (MR) study suggests a causal relationship between metformin treatment and a decrease in OP and fracture incidence, as well as an increase in bone mineral density (BMD) in the lumbar spine, femoral neck, and heel. Nonetheless, no significant causal effect is observed on forearm BMD.
PURPOSE
We utilize a MR approach to investigate the association between metformin treatment and the risk of OP.
METHODS
Metformin treatment was selected as exposures. Outcomes included OP; BMD at the forearm (FA), femoral neck (FN), and lumbar spine (LS); estimated heel bone mineral density (eBMD); and fracture. Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. Inverse variance-weighted (IVW) analysis was mainly applied; the weighted median (WM), penalized weighted median (PWM), maximum likelihood (ML), and MR-Egger regression (MR-Egger) method were also used to obtain robust estimates. A series of sensitivity analyses including Cochran's Q test, MR-Egger regression, leave-one-out analysis, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were used to detect pleiotropy or heterogeneity.
RESULTS
In the main analysis, IVW estimates demonstrated that metformin treatment had a definite causal effect on the risk of OP (odds ratio (OR): 0.859, 95% CI: 0.774-0.953, P = 0.004), LS-BMD (OR: 1.063, 95% CI: 1.023-1.105, P = 0.002), FN-BMD (OR: 1.034, 95% CI: 1.000-1.069, P = 0.049), eBMD (OR: 1.035, 95% CI: 1.023-1.047, P ≤ 0.001), and fracture(OR: 0.958, 95% CI: 0.928-0.989, P = 0.008). However, it did not have an effect on FA-BMD(OR: 1.050, 95% CI: 0.969-1.138, P = 0.237).
CONCLUSIONS
This study indicated that metformin treatment is significantly associated with a reduction in the risk of OP, fracture and higher LS-BMD, FN-BMD, and eBMD. However, there was no significant association with FA-BMD.
Topics: Metformin; Humans; Mendelian Randomization Analysis; Bone Density; Hypoglycemic Agents; Osteoporotic Fractures; Osteoporosis; Incidence; Femur Neck; Genome-Wide Association Study; Lumbar Vertebrae; Polymorphism, Single Nucleotide; Diabetes Mellitus, Type 2
PubMed: 38536446
DOI: 10.1007/s00198-023-07013-0 -
Current Opinion in Endocrinology,... Aug 2024The assessment of fracture risk is playing an ever-increasing role in osteoporosis clinical management and informing international guidelines for osteoporosis. FRAX, a... (Review)
Review
PURPOSE OF REVIEW
The assessment of fracture risk is playing an ever-increasing role in osteoporosis clinical management and informing international guidelines for osteoporosis. FRAX, a fracture risk calculator that provides individualized 10-year probabilities of hip and major osteoporotic fracture, has been widely used since 2008. In this review, we recap the development and limitations of intervention thresholds and the role of absolute fracture risk.
RECENT FINDINGS
There is an increasing awareness of disparities and inequities in the setting of intervention thresholds in osteoporosis. The limitations of the simple use of prior fracture or the DXA-derived BMD T -score threshold are increasingly being discussed; one solution is to use fracture risk or probabilities in the setting of such thresholds. This approach also permits more objective assessment of high and very high fracture risk to enable physicians to make choices not just about the need to treat but what agents to use in individual patients.
SUMMARY
Like all clinical tools, FRAX has limitations that need to be considered, but the use of fracture risk in deciding who to treat, when to treat and what agent to use is a mechanism to target treatment equitably to those at an increased risk of fracture.
Topics: Humans; Risk Assessment; Osteoporotic Fractures; Osteoporosis; Bone Density; Absorptiometry, Photon; Risk Factors; Female; Bone Density Conservation Agents
PubMed: 38809256
DOI: 10.1097/MED.0000000000000871 -
Osteoporosis International : a Journal... Mar 2024The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts.... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm.
INTRODUCTION
Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD).
METHODS
The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.
RESULTS
Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men.
CONCLUSIONS
A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.
Topics: Male; Humans; Female; Osteoporotic Fractures; Prospective Studies; Risk Assessment; Cohort Studies; Risk Factors; Bone Density; Hip Fractures
PubMed: 38228807
DOI: 10.1007/s00198-023-07012-1 -
Journal of Bone and Mineral Research :... Oct 2023Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy... (Randomized Controlled Trial)
Randomized Controlled Trial
Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: -3.72% [95% confidence interval: -5.01%, -2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Female; Osteoporosis, Postmenopausal; Bone Density Conservation Agents; Postmenopause; Osteoporosis; Bone Density; Osteoporotic Fractures; Lumbar Vertebrae; Minerals
PubMed: 37417725
DOI: 10.1002/jbmr.4877 -
Acta Biomaterialia Aug 2023Zn and its alloys are increasingly under consideration for biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical...
Metal-organic Zn-zoledronic acid and 1-hydroxyethylidene-1,1-diphosphonic acid nanostick-mediated zinc phosphate hybrid coating on biodegradable Zn for osteoporotic fracture healing implants.
Zn and its alloys are increasingly under consideration for biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for osteoporotic bone fracture healing, due to their uneven degradation mode, burst release of zinc ions, and insufficient osteo-promotion and osteo-resorption regulating properties. In this study, a type of Zn coordinated zoledronic acid (ZA) and 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) metal-organic hybrid nanostick was synthesized, which was further mixed into zinc phosphate (ZnP) solution to mediate the deposition and growth of ZnP to form a well-integrated micro-patterned metal-organic/inorganic hybrid coating on Zn. The coating protected noticeably the Zn substrate from corrosion, in particular reducing its localized occurrence as well as suppressing its Zn release. Moreover, the modified Zn was osteo-compatible and osteo-promotive and, more important, performed osteogenesis in vitro and in vivo of well-balanced pro-osteoblast and anti-osteoclast responses. Such favorable functionalities are related to the nature of its bioactive components, especially the bio-functional ZA and the Zn ions it contains, as well as its unique micro- and nano-scale structure. This strategy provides not only a new avenue for surface modification of biodegradable metals but also sheds light on advanced biomaterials for osteoporotic fracture and other applications. STATEMENT OF SIGNIFICANCE: Developing appropriate biodegradable metallic materials is of clinical relevance for osteoporosis fracture healing, whereas current strategies are short of good balance between the bone formation and resorption. Here, we designed a micropatterned metal-organic nanostick mediated zinc phosphate hybrid coating modified Zn biodegradable metal to fulfill such a balanced osteogenicity. The in vitro assays verified the coated Zn demonstrated outstanding pro-osteoblasts and anti-osteoclasts properties and the coated intramedullary nail promoted fracture healing well in an osteoporotic femur fracture rat model. Our strategy may offer not only a new avenue for surface modification of biodegradable metals but also shed light on better understanding of new advanced biomaterials for orthopedic application among others.
Topics: Rats; Animals; Zoledronic Acid; Osteoporotic Fractures; Biocompatible Materials; Phosphates; Alloys; Zinc; Absorbable Implants; Corrosion; Materials Testing
PubMed: 37196904
DOI: 10.1016/j.actbio.2023.05.020 -
Osteoporosis International : a Journal... Aug 2023This study revealed that there was no significant linear relationship between fasting C-peptide (FCP) level and bone mineral density (BMD) or fracture risk in type 2...
UNLABELLED
This study revealed that there was no significant linear relationship between fasting C-peptide (FCP) level and bone mineral density (BMD) or fracture risk in type 2 diabetes mellitus (T2DM) patients. However, in the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with whole body (WB), lumbar spine (LS), and femoral neck (FN) BMD and negatively correlated with fracture risk.
PURPOSE
To explore the relationship between C-peptide and BMD and fracture risk in T2DM patients.
METHODS
530 T2DM patients were enrolled and divided into three groups by FCP tertiles, and the clinical data were collected. BMD was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was evaluated by adjusted fracture risk assessment tool (FRAX).
RESULTS
In the FCP ≤ 1.14 ng/ml group, FCP level was positively correlated with WB, LS, and FN BMD, while FCP was negatively correlated with fracture risk and osteoporotic fracture history. However, FCP was not correlated with BMD and fracture risk and osteoporotic fracture history in the 1.14 < FCP ≤ 1.73 ng/ml and FCP > 1.73 ng/ml groups. The study has shown that FCP was an independent factor influencing BMD and fracture risk in the FCP ≤ 1.14 ng/ml group.
CONCLUSIONS
There is no significant linear relationship between FCP level and BMD or fracture risk in T2DM patients. In the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with WB, LS, and FN BMD and negatively correlated with fracture risk, and FCP is an independent influencing factor of BMD and fracture risk. The findings suggest that FCP may predict the risk of osteoporosis or fracture in some T2DM patients, which has a certain clinical value.
Topics: Humans; Bone Density; Osteoporotic Fractures; Diabetes Mellitus, Type 2; C-Peptide; Osteoporosis; Absorptiometry, Photon; Risk Factors; Risk Assessment
PubMed: 37204453
DOI: 10.1007/s00198-023-06785-9 -
International Journal of Molecular... Dec 2023Our objective was to overview the novel aspects in the field of adrenal gland neoplasms, namely, the management of bone status with respect to primary aldosteronism... (Review)
Review
Our objective was to overview the novel aspects in the field of adrenal gland neoplasms, namely, the management of bone status with respect to primary aldosteronism (PA). In the current narrative review, a PubMed study was conducted from inception until June 2023. The inclusion criteria were: human (clinically relevant) studies of any study design (at least 10 patients per study); English papers; and the following combination of key words within the title and/or abstract: "aldosterone" AND "bone", "skeleton", "osteoporosis", "fracture", "calcium", "parathyroid", "DXA", "osteocalcin", "P1NP", "alkaline phosphatase", "bone marker", "trabecular bone score", or "FRAX". The exclusion criteria were in vitro or animal studies, reviews, and case reports/series. We screened 1027 articles and finally included 23 studies (13 of case-control type, 3 cross-sectional, 5 prospective, 1 observational cohort, and 1 retrospective study). The assessments provided in these studies were as follows: nine studies addressed Dual-Energy X-ray Absorptiometry (DXA), another study pointed out a bone microarchitecture evaluation underlying trabecular bone score (TBS), and seven studies investigated the bone turnover markers (BTMs) profile. Moreover, 14 studies followed the subjects after adrenalectomy versus medical treatment, and 21 studies addressed secondary hyperparathyroidism in PA patients. According to our study on published data during a period of almost 40 years (n = 23, N = 3965 subjects aged between 38 and 64, with a mean age 56.75, and a female-to-male ratio of 1.05), a higher PTH in PA versus controls (healthy persons or subjects with essential hypertension) is expected, secondary hyperparathyroidism being associated in almost half of the adults diagnosed with PA. Additionally, mineral metabolism anomalies in PA may include lower serum calcium and higher urinary calcium output, all these three parameters being reversible under specific therapy for PA, regardless medical or surgical. The PA subgroup with high PTH seems at higher cardiovascular risk, while unilateral rather than bilateral disease was prone to this PTH anomaly. Moreover, bone mineral density (BMD) according to central DXA might show a higher fracture risk only in certain adults, TBS being a promising alternative (with a still unknown perspective of diabetes' influence on DXA-TBS results in PA). However, an overall increased fracture prevalence in PA is described in most studies, especially with respect to the vertebral site, the fracture risk that seems correctable upon aldosterone excess remission. These data recommend PA as a cause of secondary osteoporosis, a treatable one via PA intervention. There is still an area of debate the way to address BMTs profile in PA, the case's selection toward specific bone evaluation in every day practice, and further on, the understanding of the potential genetic influence at the level of bone and mineral complications in PA patients.
Topics: Adult; Humans; Male; Female; Middle Aged; Osteoporotic Fractures; Retrospective Studies; Calcium; Cross-Sectional Studies; Prospective Studies; Lumbar Vertebrae; Osteoporosis; Bone Density; Cancellous Bone; Hyperaldosteronism; Aldosterone; Adrenal Gland Neoplasms; Hyperparathyroidism, Secondary
PubMed: 38139166
DOI: 10.3390/ijms242417338 -
Archives of Osteoporosis Sep 2023This work studies the epidemiology of hip fracture in Egypt. While the incidence of hip fracture in Egypt matches that of the Mediterranean region, there was geographic...
UNLABELLED
This work studies the epidemiology of hip fracture in Egypt. While the incidence of hip fracture in Egypt matches that of the Mediterranean region, there was geographic variation in osteoporotic hip fracture incidence between the north and south of Egypt.
PURPOSE
To assess the incidence of hip fracture in Egypt, with special emphasis on the geographic and demographic variation among the Egyptian population.
METHODS
The incidence of hip fractures treated in two Egyptian FLS centers was calculated for the period of February 2022-February 2023. Demographic information was recorded for every patient on the national register. All patients completed a baseline questionnaire, had clinical evaluation, fracture risk, falls, and sarcopenia risk assessment. A DXA scan was carried out for every patient.
RESULTS
The annual incidence of low-energy hip fracture in individuals aged 40 years or more in Egypt in 2022-2023 was 123.34 per 100,000 in women and 55.19 per 100,000 in men. The incidence of hip fractures was higher in south Egypt (113.62) versus north Egypt (64.8). This was consistent for both genders. Bone mineral density was significantly (p < 0.01) lower in south Egypt at both the spine, distal forearm, as well as hip trochanters, whereas there was no significant difference between both locations in terms of the total hip and neck of the femur. Yet, falls risk, sarcopenia, as well as functional disability rates were significantly (p < 0.001) higher in the north.
CONCLUSION
In Egypt, the hip fracture incidence was higher in the south compared to the north. Several modifiable factors contribute to fragility fracture risk independent of BMD, creating complex interrelationships between BMD, risk factors, and fracture risk.
Topics: Female; Humans; Male; Egypt; Bone Density; Incidence; Sarcopenia; Hip Fractures; Osteoporotic Fractures
PubMed: 37688741
DOI: 10.1007/s11657-023-01325-8 -
American Journal of Physiology. Heart... Mar 2024Myocardial infarction (MI) and osteoporotic fracture (Fx) are two of the leading causes of mortality and morbidity worldwide. Although these traumatic injuries are... (Review)
Review
Myocardial infarction (MI) and osteoporotic fracture (Fx) are two of the leading causes of mortality and morbidity worldwide. Although these traumatic injuries are treated as if they are independent, there is epidemiological evidence linking the incidence of Fx and MI, thus raising the question of whether each of these events can actively influence the risk of the other. Atherosclerotic cardiovascular disease and osteoporosis, the chronic conditions leading to MI and Fx, are known to have shared pathoetiology. Furthermore, sustained systemic inflammation after traumas such as MI and Fx has been shown to exacerbate both underlying chronic conditions. However, the effects of MI and Fx outside their own system have not been well studied. The sympathetic nervous system (SNS) and the complement system initiate a systemic response after MI that could lead to subsequent changes in bone remodeling through osteoclasts. Similarly, SNS and complement system activation following fracture could lead to heart tissue damage and exacerbate atherosclerosis. To determine whether damaging bone-heart cross talk may be important comorbidity following Fx or MI, this review details the current understanding of bone loss after MI, cardiovascular damage after Fx, and possible shared underlying mechanisms of these processes.
Topics: Humans; Osteoporotic Fractures; Myocardial Infarction; Heart; Atherosclerosis; Chronic Disease
PubMed: 38305753
DOI: 10.1152/ajpheart.00576.2023