Postfracture survival in a population-based study of adults aged ≥66 yr: a call to action at hospital discharge.

Postfracture survival rates provide prognostic information but are rarely reported along with other mortality outcomes in adults aged ≥50 yr. The timing of survival change following a fracture also needs to be further elucidated. This population-based, matched-cohort, retrospective database study examined 98 474 patients (73% women) aged ≥66 yr with an index fracture occurring at an osteoporotic site (hip, clinical vertebral, proximal non-hip non-vertebral [pNHNV], and distal non-hip non-vertebral [dNHNV]) from 2011 to 2015, who were matched (1:1) to nonfracture individuals based on sex, age, and comorbidities. All-cause 1- and 5-yr overall survival and relative survival ratios (RSRs) were assessed, and time trends in survival changes were characterized starting immediately after a fracture. In both sexes, overall survival was markedly decreased over 6 yr of follow-up after hip, vertebral, and pNHNV fractures, and as expected, worse survival rates were observed in older patients and males. The lowest 5-yr RSRs were observed after hip fractures in males (66-85 yr, 51.9%-63.9%; ≥86 yr, 34.5%), followed by vertebral fractures in males (66-85 yr, 53.2%-69.4%; ≥86 yr, 35.5%), and hip fractures in females (66-85 yr, 69.8%-79.0%; ≥86 yr, 52.8%). Although RSRs did not decrease as markedly after dNHNV fractures in younger patients, relatively low 5-yr RSRs were observed in females (75.9%) and males (69.5%) aged ≥86 yr. The greatest reduction in survival occurred within the initial month after hip, vertebral, and pNHNV fractures, indicating a high relative impact of short-term factors, with survival-reduction effects persisting over time. Therefore, the most critical period for implementing interventions aimed at improving post-fracture prognosis appears to be immediately after a fracture; however, considering the immediate need for introducing such interventions, primary fracture prevention is also crucial to prevent the occurrence of the initial fracture in high-risk patients.

Sedentary behavior does not predict low BMD nor fracture-population-based Canadian Multicentre Osteoporosis Study.

Sedentary behavior (SB) or sitting is associated with multiple unfavorable health outcomes. Bone tissue responds to imposed gravitational and muscular strain with there being some evidence suggesting a causal link between SB and poor bone health. However, there are no population-based data on the longitudinal relationship between SB, bone change, and incidence of fragility fractures. This study aimed to examine the associations of sitting/SB (defined as daily sitting time), areal BMD (by DXA), and incident low trauma (fragility) osteoporotic fractures (excluding hands, feet, face, and head). We measured baseline (1995-7) and 10-yr self-reported SB, femoral neck (FN), total hip (TH), and lumbar spine (L1-L4) BMD in 5708 women and 2564 men aged 25 to 80+ yr from the population-based, nationwide, 9-center Canadian Multicentre Osteoporosis Study. Incident 10-yr fragility fracture data were obtained from 4624 participants; >80% of fractures were objectively confirmed by medical records or radiology reports. Vertebral fractures were confirmed by qualitative morphological methods. All analyses were stratified by sex. Multivariable regression models assessed SB-BMD relationships; Cox proportional models were fit for fracture risk. Models were adjusted for age, height, BMI, physical activity, and sex-specific covariates. Women in third/fourth quartiles had lower adjusted FN BMD versus women with the least SB (first quartile); women in the SB third quartile had lower adjusted TH BMD. Men in the SB third quartile had lower adjusted FN BMD than those in SB first quartile. Neither baseline nor stable 10-yr SB was related to BMD change nor to incident fragility fractures. Increased sitting (SB) in this large, population-based cohort was associated with lower baseline FN BMD. Stable SB was not associated with 10-yr BMD loss nor increased fragility fracture. In conclusion, habitual adult SB was not associated with subsequent loss of BMD nor increased risk of fracture.

The number of hours of sitting in a day (often called "sedentary behavior") is currently understood to be "bad for bone health" both because of increased bone loss and a higher risk for fractures. Very few studies in randomly sampled men and women from a whole population have consistently asked about hours of sitting and examined baseline bone density. Fewer still have compared hours of sitting and its changes over 10 yr with changes in bone density and the number of new fractures that occurred. The Canadian Multicentre Osteoporosis Study obtained sitting hours from 5708 women and 2564 men aged 25 to 80+ yr and compared it with the spine, total hip (TH), and femoral neck (FN) bone density values. The average sitting at 7.4 h in men was associated with slightly lower adjusted femoral neck bone density; in women, sitting 6.7 h/d was associated with slightly lower adjusted FN and TH bone density. Ten-year follow-up data (now in about 5000 people) showed no relationship between the slightly longer sitting (an increase of 18% in men and 22% in women) and bone loss or new bone fractures. In this large country-wide population-based study, hours of sitting each day were not associated with 10-yr BMD loss in women or men nor did sitting more associate with new bone fractures. These data are reassuring; women and men who walk regularly and have some moderate-vigorous physical activity each day, despite more sitting, do not seem to be at greater risk for osteoporosis.

Correction: Associations between Social Isolation Index and changes in grip strength, gait speed, bone mineral density (BMD), and self-reported incident fractures among older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

[This corrects the article DOI: 10.1371/journal.pone.0292788.].

Opportunistic Screening of Low Bone Mineral Density From Standard X-Rays.

BACKGROUND: Osteoporosis, characterized by loss of bone mineral density (BMD), is underscreened. Osteoporosis and low bone mass are diagnosed by a BMD T-score ≤ -2.5, and between -1.0 and -2.5, respectively, at the femoral neck or lumbar vertebrae (L1-4), using dual energy x-ray absorptiometry (DXA). The ability to estimate BMD at those anatomic sites from standard radiographs would enable opportunistic screening of low BMD (T-score < -1) in individuals undergoing x-ray for any clinical indication. METHODS: Radiographs of the lumbar spine, thoracic spine, chest, pelvis, hand, and knee, with a paired DXA acquired within 1 year, were obtained from community imaging centers (62,023 x-ray-DXA pairs of patients). A software program called Rho was developed that uses x-ray, age, and sex as inputs, and outputs a score of 1 to 10 that corresponds with the likelihood of low BMD. The program's performance was assessed using receiver-operating characteristic analyses in three independent test sets, as follows: patients from community imaging centers (n = 3,729; 83% female); patients in the Canadian Multicentre Osteoporosis Study (n = 1,780; 71% female); and patients in the Osteoarthritis Initiative (n = 591; 50% female). RESULTS: The areas under the receiver-operating characteristic curves were 0.89 (0.87-0.90), 0.87 (0.85-0.88), and 0.82 (0.79-0.85), respectively, and subset analyses showed similar results for each sex, body part, and race. CONCLUSION: Rho can opportunistically screen patients at risk of low BMD (at femoral neck or L1-4) from radiographs of the lumbar spine, thoracic spine, chest, pelvis, hand, or knee.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Associations between Osteosarcopenia and Falls, Fractures, and Frailty in Older Adults: Results From the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: To explore if older adults with osteosarcopenia are at a greater risk of falls, fractures, frailty, and worsening life satisfaction and activities of daily living (ADL) compared to those with normal bone mineral density (BMD) and without sarcopenia. DESIGN: The baseline and 3-year follow-up of a longitudinal study. SETTING AND PARTICIPANTS: Community-dwelling people aged 65 years or older in Canada. METHODS: Caucasian participants 65 years or older that completed the Canadian Longitudinal Study on Aging (CLSA) 2015 baseline interview, physical measurements and 3-year follow-up were included. Osteopenia/osteoporosis was defined as BMD T score below -1 SD according to the World Health Organization, and sarcopenia was defined as low grip strength and/or low gait speed according to the Sarcopenia Definition Outcomes Consortium. Osteosarcopenia was defined as the coexistence of osteopenia/osteoporosis and sarcopenia. Self-reported incident falls and fractures in the last 12 months before the 3-year follow-up were measured. Frailty was assessed through the Rockwood Frailty Index (FI); life satisfaction through the Satisfaction With Life Scale (SWLS); and ADL through the Older American Resources and Services modules. Multivariable logistic and linear regression, including subgroup analyses by sex, were conducted. RESULTS: The sample of 8888 participants (49.1% females) had a mean age (SD) of 72.7 (5.6) years. At baseline, neither osteopenia/osteoporosis nor sarcopenia (reference group) was present in 30.1%, sarcopenia only in 18.4%, osteopenia/osteoporosis only in 29.2%, and osteosarcopenia in 22.3%. Osteosarcopenia was significantly associated with incident falls and fractures in males [adjusted odds ratio (aOR), 1.90, 95% CI 1.15, 3.14, and aOR 2.60, 95% CI 1.14, 5.91, respectively] compared to males without osteopenia/osteoporosis or sarcopenia. Participants with osteosarcopenia had worsening ADL of 0.110 (estimated ß coefficient 0.110, 95% CI 0.029, 0.192) and a decrease in their SWLS by 0.660 (estimated ß coefficient -0.660, 95% CI -1.133, -0.187), compared to those without. Osteosarcopenia was not associated with frailty for both males and females. CONCLUSIONS AND IMPLICATIONS: Osteosarcopenia was associated with self-reported incident falls and fractures in males and worse life satisfaction and ADL for all participants. Assessing and identifying osteosarcopenia is essential for preventing falls and fractures. Furthermore, it improves life satisfaction and ADL.

The effect of femur positioning on dual-energy X-ray absorptiometry (DXA) measures and statistical shape and appearance modeling (SSAM) fracture risk assessments.

The diagnosis of osteoporosis using Dual-energy X-ray Absorptiometry (DXA) relies on accurate hip scans, whereby variability in measurements may be introduced by altered patient positioning, as could occur with repeated scans over time. The goal herein was to test how altered postures affect diagnostic metrics (i.e., standard clinical metrics and a newer image processing tool) for femur positioning. A device was built to support cadaveric femurs and adjust their orientation in 3° increments in flexion and internal/external rotation. Seven isolated femurs were scanned in six flexion postures (0° (neutral) to 15° of flexion) and eleven rotational postures (15° external to 15° internal rotation) while collecting standard clinical DXA-based measures for each scan. The fracture risk tool was applied to each scan to calculate fracture risk. Two separate one-way repeated measures ANOVAs (α = 0.05) were performed on the DXA-based measures and fracture risk prediction output. Flexion had a significant effect on T-score, Bone Mineral Density (BMD), and Bone Mineral Content (BMC), but not area, at angles greater than 12°. Internal and external rotation did not have a significant effect on any clinical metric. Fracture risk (as assessed by the image processing tool) was not affected by either rotation mode. Overall, this suggests clinicians can adjust patient posture to accommodate discomfort if deviations are less than 12 degrees, and the greatest care should be taken in flexion. Furthermore, the tool is relatively insensitive to postural adjustments, and as such may be a good option for tracking risk over repeated patient scans.

Associations between Social Isolation Index and changes in grip strength, gait speed, bone mineral density (BMD), and self-reported incident fractures among older adults: Results from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: The aim is to investigate whether social isolation and loneliness are associated with changes in grip strength, gait speed, BMD, and fractures. METHODS: Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort participants aged 65 years and older at baseline (2012-2015) who completed the three-year follow-up interview (2015-2018) were included in this analysis (n = 11,344). Social isolation and loneliness were measured using the CLSA social isolation index (CLSA-SII, range 0-10). We calculated absolute and percent change in grip strength (kg) and gait speed (m/s) and annualized absolute (g/cm2) and percent change in femoral neck and total hip BMD during the three-year follow-up. Self-reported incident fractures of all skeletal sites in the previous 12 months were measured at three-year follow-up. Multivariable analyses were conducted. Odd ratio (OR) and 95% confidence interval (CI) are reported. RESULTS: The mean age (standard deviation [SD]) was 72.9 (5.6) years and 49.9% were female. The mean (SD) of CLSA-SII at baseline was 3.5 (1.4). Mean absolute and percentage change (SD) in grip strength (kg) and gait speed (m/s) were -1.33 (4.60), -3.02% (16.65), and -0.05 (0.17), -3.06% (19.28) during the three-year follow-up, respectively. Mean annualized absolute (g/cm2) and percentage change (SD) in femoral neck and total hip BMD were -0.004 (0.010), -0.47% (1.43) and -0.005 (0.009), -0.57% (1.09), respectively. 345 (3.1%) participants had incident fractures. As CLSA-SII increased (per one unit change), participants had 1.13 (adjusted OR 1.13, 95% CI 1.01-1.27) times greater odds for incident fractures. The interaction term between the CLSA-SII and centre for epidemiology studies depression 9 scale (CES-D 9) for self-reported incident fractures was shown (interaction OR 1.02, 95% CI 1.00-1.04). CONCLUSIONS: Socially isolated and lonely older adults were more likely to have had incident fractures, but social isolation was not associated with the three-year changes in grip strength, gait speed, or BMD.

Effect of Vitamin D3 Supplementation on Acute Fracture Healing: A Phase II Screening Randomized Double-Blind Controlled Trial.

Nearly half of adult fracture patients are vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Many surgeons advocate prescribing vitamin D supplements to improve fracture healing outcomes; however, data supporting the effectiveness of vitamin D3 supplements to improve acute fracture healing are lacking. We tested the effectiveness of vitamin D3 supplementation for improving tibia and femur fracture healing. We conducted a single-center, double-blinded phase II screening randomized controlled trial with a 12-month follow-up. Patients aged 18-50 years receiving an intramedullary nail for a tibia or femoral shaft fracture were randomized 1:1:1:1 to receive (i) 150,000 IU loading dose vitamin D3 at injury and 6 weeks (n = 27); (ii) 4000 IU vitamin D3 daily (n = 24); (iii) 600 IU vitamin D3 daily (n = 24); or (iv) placebo (n = 27). Primary outcomes were clinical fracture healing (Function IndeX for Trauma [FIX-IT]) and radiographic fracture healing (Radiographic Union Score for Tibial fractures [RUST]) at 3 months. One hundred two patients with a mean age of 29 years (standard deviation 8) were randomized. The majority were male (69%), and 56% were vitamin D3 deficient at baseline. Ninety-nine patients completed the 3-month follow-up. In our prespecified comparisons, no clinically important or statistically significant differences were detected in RUST or FIX-IT scores between groups when measured at 3 months and over 12 months. However, in a post hoc comparison, high doses of vitamin D3 were associated with improved clinical fracture healing relative to placebo at 3 months (mean difference [MD] 0.90, 80% confidence interval [CI], 0.08 to 1.79; p = 0.16) and within 12 months (MD 0.89, 80% CI, 0.05 to 1.74; p = 0.18). The study was designed to identify potential evidence to support the effectiveness of vitamin D3 supplementation in improving acute fracture healing. Vitamin D3 supplementation, particularly high doses, might modestly improve acute tibia or femoral shaft fracture healing in healthy adults, but confirmatory studies are required. The Vita-Shock trial was awarded the Orthopaedic Trauma Association's (OTA) Bovill Award in 2020. This award is presented annually to the authors of the most outstanding OTA Annual Meeting scientific paper. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Association Among Cognition, Frailty, and Falls and Self-Reported Incident Fractures: Results From the Canadian Longitudinal Study on Aging (CLSA).

Cognition, frailty, and falls have been examined independently as potential correlates of fracture risk, but not simultaneously. Our objective was to explore the association between cognition, frailty, and falls and self-reported incident fractures to determine if these factors show significant independent associations or interactions. We included participants who completed the Canadian Longitudinal Study on Aging (CLSA) 2012-2015 baseline comprehensive assessment, did not experience any self-reported fractures in the year prior to cohort recruitment, and completed the follow-up questionnaire at year 3 (n = 26,982). We compared all baseline cognitive measures available in the CLSA, the Rockwood Frailty Index (FI), and presence of self-reported falls in the past 12 months in those with versus without self-reported incident fractures in year 3 of follow-up. We used multivariable logistic regression adjusted for covariates and examined two-way interactions between cognition, frailty, and prior falls. CLSA specified analytic weights were applied. The mean ± standard error (SE) age of participants was 59.5 ± 0.1 years and 52.2% were female. A total of 715 participants (2.7%) self-reported incident fractures at 3-year follow-up. Participants who experienced incident fractures had similar baseline cognition scores (mean ± SE; Rey Auditory Verbal Learning Test [RAVLT]: Immediate recall 6.1 ± 0.1 versus 5.9 ± 0.0; standardized difference [d] 0.124); higher FI scores (mean ± SE; FI 0.134 ± 0.005 versus 0.116 ± 0.001; d 0.193), and a greater percentage had fallen in the past 12 months (weighted n [%] 518 [7.2] versus 919 [3.5]; d 0.165). FI (each increment of 0.08) was associated with a significantly increased risk of self-reported incident fractures in participants of all ages and those aged 65 years or older (adjusted odd ratio [OR] 1.24, 95% confidence limit [CL] 1.10-1.40; adjusted OR 1.44, 95% CL 1.11-1.52, respectively). The adjusted odds for self-reported incident fractures in participants of all ages was also significantly associated with falls in the past 12 months prior to baseline (adjusted OR 1.83; 95% CL 1.13-2.97), but not in those aged 65 years or older. No interactions between cognition, frailty, and prior falls were found. However, considering the relatively young age of our cohort, it may be appropriate to make strong inferences in individuals older than 65 years of age. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Clinical Considerations in the Selection of Preexposure Prophylaxis for HIV Prevention in Canada.

According to the Public Health Agency of Canada, approximately 62,050 people were living with HIV in Canada in 2018, and of those, 13% were undiagnosed. Currently, no single strategy provides complete protection or is universally effective across all demographic groups at risk for HIV. However, HIV preexposure prophylaxis (PrEP) is the newest HIV prevention strategy that shows promise. To date, two products have received an indication for PrEP by Health Canada: emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) and emtricitabine/tenofovir alafenamide (Descovy®; FTC/TAF). Despite the high efficacy of these PrEP intervention methods, access to PrEP in Canada remains low. Identifying and addressing barriers to PrEP access, especially in high-risk groups, are necessary to reduce HIV transmission in Canada. While guidelines published by the Center for Disease Control and Prevention (CDC) include FTC/TAF information, the efficacy of FTC/TAF for PrEP has not yet been considered in Canada's clinical practice guidelines. Thus, the current paper reviews data regarding the use of FTC/TDF and FTC/TAF for PrEP, which may be useful for Canadian healthcare providers when counseling and implementing HIV prevention methods. The authors highlight these data in relation to various at-risk populations and review ongoing clinical trials investigating novel PrEP agents. Overall, FTC/TDF PrEP is effective for many populations, including men who have sex with men, transgender women, heterosexuals with partners living with HIV, and people who use drugs. While there is fewer data reported on the efficacy of FTC/TAF to date, recent clinical trials have demonstrated noninferiority of FTC/TAF in comparison to FTC/TDF. Notably, as studies have shown that FTC/TAF maintains renal function and bone mineral density to a greater extent than FTC/TDF, FTC/TAF may be a safer option for patients experiencing renal and/or bone dysfunction, for those at risk of renal and bone complications, and for those who develop FTC/TDF-related adverse events.

Associations between glycated hemoglobin and the risks of incident cardiovascular diseases in patients with gout.

BACKGROUND: Evidence for the relationship between glycated hemoglobin (HbA1c) levels and risk of cardiovascular diseases (CVD) in patients with gout remained sparse and limited. This study aims to explore the associations between HbA1c levels and risks of incident CVD in patients with gout. METHODS: We included patients with gout who had an HbA1c measurement at baseline from the UK Biobank. CVD events were identified from through medical and death records. We used multivariable Cox proportional hazards model with a restricted cubic spline to assess the potential non-linear effect of HbA1c on CVD risk. RESULTS: We included a total of 6,685 patients (mean age 59.7; 8.1% females) with gout for analyses. During a mean follow-up of 7.3 years, there were 1,095 CVD events documented with an incidence of 2.26 events per 100 person-years (95% confidence interval [CI]: 2.13-2.40). A quasi J-shaped association between HbA1c and risk of CVD was observed, with the potentially lowest risk found at the HbA1c of approximately 5.0% (hazard ratio [HR] = 0.65, 95% CI: 0.53-0.81). When compared with the HbAlc level of 7%, a significantly decreased risk of CVD was found from 5.0 to 6.5%, while an increased risk was observed at 7.5% (HR = 1.05) and 8.0% (HR = 1.09). Subgroup analyses yielded similar results to the main findings in general. CONCLUSIONS: Based on data from a nationwide, prospective, population-based cohort, we found a quasi J-shaped relationship between HbA1c and risk of CVD in patients with gout. More high-quality evidence is needed to further clarify the relationship between HbA1c and CVD risk in patients with gout.

Relationship between Serum 25-Hydroxyvitamin D Level and Risk of Recurrent Stroke.

Evidence for the association between vitamin D and risk of recurrent stroke remains sparse and limited. We aimed to assess the relationship between serum circulating 25-hydroxyvitamin D (25(OH)D) level and risk of recurrent stroke in patients with a stroke history, and to identify the optimal 25(OH)D level in relation to lowest recurrent stroke risk. Data from the nationwide prospective United Kingdom Biobank were used for analyses. Primary outcome was time to first stroke recurrence requiring a hospital visit during follow-up. We used Cox proportional hazards regression model with restricted cubic splines to explore 25(OH)D level in relation to recurrent stroke. The dose-response relationship between 25(OH)D and recurrent stroke risk was also estimated, taking the level of 10 nmol/L as reference. A total of 6824 participants (mean age: 60.6 years, 40.8% females) with a baseline stroke were included for analyses. There were 388 (5.7%) recurrent stroke events documented during a mean follow-up of 7.6 years. Using Cox proportional hazards regression model with restricted cubic splines, a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke was found, where the lowest recurrent stroke risk lay at the 25(OH)D level of approximate 60 nmol/L. When compared with 10 nmol/L, a 25(OH)D level of 60 nmol/L was related with a 48% reduction in the recurrent stroke risk (hazard ratio = 0.52, 95% confidence interval: 0.33-0.83). Based on data from a large-scale prospective cohort, we found a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke in patients with a stroke history. Given a lack of exploring the cause-effect relationship in this observational study, more high-quality evidence is needed to further clarify the vitamin D status in relation to recurrent stroke risk.

Efficacy and Safety of Romosozumab Among Postmenopausal Women With Osteoporosis and Mild-to-Moderate Chronic Kidney Disease.

Patients with osteoporosis and chronic kidney disease (CKD) are at increased risk of fracture and associated negative outcomes, including increased mortality. The present post hoc analysis of two randomized, multicenter, phase 3 clinical trials-Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) and Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH)-investigated the efficacy and safety of romosozumab in postmenopausal women with osteoporosis and mild-to-moderate CKD. The analysis included data from 7147 patients from FRAME and 4077 from ARCH. Eighty-one percent of patients from FRAME and 85% from ARCH had mild or moderate reduction in estimated glomerular filtration rate (eGFR) at baseline, and part of this reduction is likely age related. During the 1-year double-blind phases of the trials, patients received romosozumab 210 mg sc or placebo monthly in FRAME and romosozumab 210 mg sc monthly or alendronate 70 mg po weekly in ARCH. Bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck and vertebral and nonvertebral fractures were assessed at baseline and month 12. In both trials, the least-square mean percent change from baseline BMD was significantly greater in the romosozumab groups versus controls across all kidney function categories at month 12. Romosozumab reduced the relative risk of new vertebral fractures at month 12 among patients with eGFR of 30-59, 60-89, and ≥90 mL/min by 72% (95% confidence interval [CI] 14-91; p = 0.017), 70% (40-85; p < 0.001), and 84% (30-96; p = 0.005), respectively, in FRAME versus placebo, and by 51% (5-75; p = 0.04), 19% (-28 to 49; p = 0.39), and 57% (1-81, p = 0.04), respectively, in ARCH versus alendronate. Incidences of adverse events, asymptomatic decreases in serum calcium, and evolution of kidney function during the studies were similar across all baseline kidney function groups. Romosozumab is an effective treatment option for postmenopausal women with osteoporosis and mild-to-moderate reduction in kidney function, with a similar safety profile across different levels of kidney function. © 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).

Trends in risk factor control in patients with gout: data from the National Health and Nutrition Examination Survey, 2007-2018.

OBJECTIVES: To explore trends in risk factor control (hypertension, diabetes mellitus, hyperlipidaemia) in patients with gout and medication use among those whose risk factor control targets were not achieved. METHODS: We used the data from National Health and Nutrition Examination Survey (NHANES) between 2007-2008 and 2017-2018 for analyses. The study samples were weighted so that they could be representative of the non-institutionalized US population. We conducted a cross-sectional analysis to assess trends in risk factor control and medication use, and employed logistic regression analyses to explore patient characteristics associated with risk factor control. RESULTS: The prevalence of participants in whom blood pressure control target was achieved decreased from 64.6% in 2007-2008 to 55.3% in 2017-2018 (P-value for trend = 0.03). The percentage of participants whose glycaemic, lipid or all three risk factor control targets were achieved remained stable temporally (P > 0.05). Some patient characteristics were significantly related to risk factor control, including age 45-64, age ≥65, Asian Americans, non-Hispanic Blacks, higher family income, and being overweight and obese. A trend towards increased use of glucose-lowering medication was found (from 71.0% in 2007-2008 to 94.7% in 2017-2018, P < 0.01), while the prevalence of taking blood pressure-lowering and lipid-lowering medications remained stable (P > 0.05). CONCLUSION: Based on NHANES data, a significant trend towards decreased blood pressure control was observed in patients with gout, while glycaemic and lipid control levelled off. These findings emphasize that more endeavours are needed to improve management of cardiovascular risk factors in patients with gout.

Birth Weight and the Risk of Cardiovascular Outcomes: A Report From the Large Population-Based UK Biobank Cohort Study.

Background: Birth weight has been reported to be associated with the risk of incident cardiovascular disease (CVD); however, the relationship remains inconclusive. Here, we aimed to prospectively assess the associations between birth weight and CVD risk using the data from UK Biobank, a large-scale, prospective cohort study. Methods: We included 270,297 participants who were free of CVD at baseline and reported their birth weight for analyses. The primary outcome was incident CVD. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were calculated using Cox proportional hazards models adjusted for potential confounding variables. Results: During a median follow-up of 8.07 years (IQR: 7.4-8.7 years), 10,719 incident CVD events were recorded. The HRs for low birth weight vs. normal birth weight (2.5-4.0 kg) were 1.23 (95% CI: 1.09-1.38) for risk of incident CVD, 1.52 (95% CI: 1.18-1.95) for stroke, 1.33 (95% CI: 1.07-1.64) for myocardial infarction, and 1.15 (95% CI: 1.01-1.32) for CHD. For the ones with low birth weight, the risk of CVD is reduced by 11% for every kilogram of birth weight gain. The association of low birth weight with CVD was stronger among those younger than 55 years (p = 0.001). No association between high birth weight and risk of cardiovascular outcomes was found. Conclusion: Low birth weight was associated with an increased risk of cardiovascular events. These findings highlight the longstanding consequence of low birth weight on cardiovascular system.

The reporting and handling of missing data in longitudinal studies of older adults is suboptimal: a methodological survey of geriatric journals.

BACKGROUND: Missing data are common in longitudinal studies, and more so, in studies of older adults, who are susceptible to health and functional decline that limit completion of assessments. We assessed the extent, current reporting, and handling of missing data in longitudinal studies of older adults. METHODS: Medline and Embase databases were searched from 2015 to 2019 for publications on longitudinal observational studies conducted among persons ≥55 years old. The search was restricted to 10 general geriatric journals published in English. Reporting and handling of missing data were assessed using questions developed from the recommended standards. Data were summarised descriptively as frequencies and proportions. RESULTS: A total of 165 studies were included in the review from 7032 identified records. In approximately half of the studies 97 (62.5%), there was either no comment on missing data or unclear descriptions. The percentage of missing data varied from 0.1 to 55%, with a 14% average among the studies that reported having missing data. Complete case analysis was the most common method for handling missing data with nearly 75% of the studies (n = 52) excluding individual observations due to missing data, at the initial phase of study inclusion or at the analysis stage. Of the 10 studies where multiple imputation was used, only 1 (10.0%) study followed the guideline for reporting the procedure fully using online supplementary documents. CONCLUSION: The current reporting and handling of missing data in longitudinal observational studies of older adults are inadequate. Journal endorsement and implementation of guidelines may potentially improve the quality of missing data reporting. Further, authors should be encouraged to use online supplementary files to provide additional details on how missing data were addressed, to allow for more transparency and comprehensive appraisal of studies.

An update of the prevalence of osteoporosis, fracture risk factors, and medication use among community-dwelling older adults: results from the Canadian Longitudinal Study on Aging (CLSA).

The prevalence of self-reported and DXA-confirmed osteoporosis was 7.8% (males 2.2%; females 12.7%), and 3.6% (males 1.2%; females 5.9%), respectively. We found that most community-dwelling older adults at high fracture risk are not taking osteoporosis medication, particularly males. There is a major opportunity for improved primary fracture prevention in the community. PURPOSE: To provide an up-to-date prevalence estimate of osteoporosis, fracture risk factors, fracture risk, and the proportion of older Canadians at high fracture risk who are not taking an osteoporosis medication. METHODS: We included Canadian Longitudinal Study on Aging (CLSA) participants: a community-dwelling cohort aged 45 to 85 years who completed the baseline (2015) comprehensive interview and had dual-energy X-ray absorptiometry (DXA) scans (N = 30,097). We describe the age- and sex-stratified prevalence of (1) self-reported osteoporosis; (2) DXA-confirmed osteoporosis; (3) fracture risk factors and people who are at high risk (FRAX® major osteoporotic fracture probability ≥ 20%); and (4) people who are at high fracture risk not taking osteoporosis medications. Sampling weights, as defined by the CLSA, were applied. RESULTS: The mean age of participants was 70.0 (SD 10.3). Overall, 7.8% had self-reported osteoporosis (males 2.2%; females 12.7%) while 3.6% had DXA-confirmed osteoporosis (males 1.2%; females 5.9%), and 2.8% were at high fracture risk (males 0.3%; females 5.1%). Of people who had osteoporosis and were at high risk, 77.3% were not taking an osteoporosis medication (males 92.3%; females 76.8%). CONCLUSIONS: Our study provides an up-to-date prevalence estimate of osteoporosis for community-dwelling older Canadians. We found that most community-dwelling older adults at high fracture risk are not taking an osteoporosis medication, particularly males. There is a major opportunity for improved primary fracture prevention in the community.

Hip fracture predicts subsequent hip fracture: a retrospective observational study to support a call to early hip fracture prevention efforts in post-fracture patients.

In this real-world retrospective cohort, subsequent hip fracture occurred in one in four patients with any initial fracture, most often after hip fracture, on average within 1.5 years. These data support the need for early post-fracture interventions to help reduce imminent hip fracture risk and high societal and humanistic costs. PURPOSE: This large retrospective cohort study aimed to provide hip fracture data, in the context of other fractures, to help inform efforts related to hip fracture prevention focusing on post-fracture patients. METHODS: A cohort of 115,776 patients (72.3% female) aged > 65 (median age 81) with an index fracture occurring at skeletal sites related to age-related bone loss between January 1, 2011, and March 31, 2015, was identified using health services data from Ontario, Canada, and followed until March 31, 2017. RESULTS: Hip fracture was the most common second fracture (27.8%), occurring in ≥ 19% of cases after each index fracture site and most frequently (33.0%) after hip index fracture. Median time to a second fracture of the hip was ~ 1.5 years post-index event. Patients with index hip fracture contributed the most to fracture-related initial surgeries (64.1%) and post-surgery complications (71.9%) and had the second-highest total mean healthcare cost per patient in the first year after index fracture ($62,793 ± 44,438). One-year mortality (any cause) after index hip fracture was 26.2% vs. 15.9% in the entire cohort, and 25.9% after second hip fracture. CONCLUSION: A second fracture at the hip was observed in one in four patients after any index fracture and in one in three patients with an index hip fracture, on average within 1.5 years. Index hip fracture was associated with high mortality and post-surgery complication rates and healthcare costs relative to other fractures. These data support focusing on early hip fracture prevention efforts in post-fracture patients.