Early-onset dementia and risk of hip fracture and major osteoporotic fractures.

INTRODUCTION: There is limited knowledge about early-onset dementia (EOD) on fracture risk. METHODS: Individuals ages 50 to 64 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (2012 to 2019). The association between EOD and fractures and the association between cholinesterase inhibitors for EOD and fractures were evaluated using logistic regression analyses. RESULTS: We identified 13,614 EOD patients and 9,144,560 cognitively healthy individuals. The analysis revealed that EOD was associated with an increased risk of hip fractures (adjusted odds ratio, 95% confidence interval: 8.79, 7.37-10.48), vertebral fractures (1.73, 1.48-2.01), and major osteoporotic fractures (2.05, 1.83-2.30) over 3 years. The use of cholinesterase inhibitors was significantly associated with a reduction in hip fractures among EOD patients (0.28, 0.11-0.69). DISCUSSION: EOD patients have a higher risk of osteoporotic fractures than cognitively healthy individuals. The use of cholinesterase inhibitors may reduce the risk of hip fracture among EOD patients. HIGHLIGHTS: It is unknown whether early-onset dementia (EOD) increases the risk of fractures. We identified 13,614 individuals with EOD using a nationwide administrative database. Patients with EOD have a higher risk of hip, vertebral, and major osteoporotic fractures. The use of cholinesterase inhibitors may reduce hip fracture among patients with EOD.

Association between pharmacotherapy and secondary vertebral fracture managed with a brace in a real-world setting: A nationwide database study in Japan.

AIM: This retrospective cohort study assessed the association between the incidence of secondary vertebral fracture managed with a brace (SVF) and pharmacotherapy. METHODS: The association between the incidence of SVF and the presence, type, and medication possession ratio (MPR) of pharmacotherapy was investigated using medical insurance data acquired from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: The data of female patients (n = 637 303) were analyzed. The 2-year incidence of SVF was 73.5 per 10 000 patients (n = 4687). Approximately 0.73% of patients without medications and 0.74% with medications had SVF. Patients taking bisphosphonates (0.87), denosumab (0.77), and selective estrogen receptor modulators (0.88) had significantly lower standardized incidence ratios (SIRs) than patients not taking medications after the occurrence of primary fracture; meanwhile, patients taking parathyroid hormone medications had considerably higher SIRs than those not taking medications. The non-SVF group (59.1%) had a significantly higher mean MPR than the SVF group (55.5%). Patients taking denosumab in the non-SVF group (68.2%) had the highest mean MPR. The proportion of patients taking denosumab with an MPR of ≥80% in the non-SVF group was significantly higher than that in the SVF group. CONCLUSION: Patients taking medications were at a lower risk of developing SVF than those not taking medications. Although this study did not compare the medications' SVF prevention effects, patients taking denosumab had a 0.77 SIR of SVF in Japan. The effect of pharmacotherapy on SVF prevention might be affected by the MPR of each medication. Geriatr Gerontol Int 2024; 24: 390-397.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

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.

Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90 days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide health insurance claims database in Japan.

PURPOSE: Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90 days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC (≥ 70 mg prednisolone or equivalent; PSL) in the initial 90 days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080 days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. RESULTS: We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90 days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC ≥ 5 mg PSL/day had a significantly increased fracture risk in the stratum of 30-59 days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5 mg PSL/day) for 90 days in the initial 90 days of GC therapy had a significantly increased fracture risk. CONCLUSIONS: GC exposure in the initial 90 days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90 days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.

Association between the 110-kDa C-terminal agrin fragment and skeletal muscle decline among community-dwelling older women.

BACKGROUND: C-terminal agrin fragment (CAF) is a biomarker for neuromuscular junction degradation. This study aimed to investigate whether 110-kDa CAF (CAF110) was associated with the presence and incidence of low muscle mass and strength. METHODS: This cross-sectional retrospective cohort study comprised women aged ≥65 years. We measured muscle mass using a dual-energy X-ray absorptiometry scanner, hand-grip strength, and blood sampling between 2011 and 2012. A follow-up study with the same measurements was conducted between 2015 and 2017. Low muscle mass and strength were defined as an appendicular skeletal muscle mass index <5.4 kg/m2 and hand-grip strength <18 kg, respectively. The CAF110 level was measured using enzyme-linked immunosorbent assay kits. RESULTS: In total, 515 women (74.3 ± 6.3 years) were included in this cross-sectional analysis. Of these, 101 (19.6%) and 128 (24.9%) women presented with low muscle mass and strength, respectively. For low muscle mass, the odds ratios (ORs) of the middle and highest CAF110 tertile groups, compared with the lowest group, were 1.93 (95% confidence interval: 1.09-3.43; P = 0.024) and 2.15 (1.22-3.80; P = 0.008), respectively. After adjusting for age, the ORs remained significant: 1.98 (1.11-3.52; P = 0.020) and 2.27 (1.28-4.03; P = 0.005), respectively. Low muscle strength ORs of all the CAF110 tertile groups were not significant. In the longitudinal analysis, 292 and 289 women were assessed for incidents of low muscle mass and strength, respectively. Of those, 34 (11.6%) and 20 (6.9%) women exhibited low muscle mass and strength, respectively. For incident low muscle mass, the crude OR of the CAF110 ≥ the median value group was marginally higher than that of the CAF110 < median value group (median [interquartile range]: 1.98 [0.94-4.17] (P = 0.072). After adjusting for age and baseline muscle mass, the OR was 2.22 [0.97-5.06] (P = 0.058). All low muscle strength ORs of the median categories of CAF110 were not significant. CONCLUSIONS: CAF110 was not associated with low muscle strength. However, CAF110 may be a potential marker for the incidence of low muscle mass.

Prescription of vitamin D was associated with a lower incidence of hip fractures.

Patients with osteoporosis are prone to fragility fractures. Evidence of the effects of active forms of vitamin D on hip fracture prevention is insufficient. We examined the association between vitamin D prescription and incidence of new fractures using the data of osteoporotic patients from the nationwide health insurance claims database of Japan. The follow-up period was 3 years after entry. The untreated patients were never prescribed vitamin D during follow-up (n = 422,454), and the treated patients had a vitamin D medication possession ratio of ≥ 0.5 at all time points (n = 169,774). Propensity score matching was implemented on these groups, yielding 105,041 pairs, and subsequently, the control and treatment groups were established and analyzed. The incidence of new fractures was significantly lower in the treatment group compared with the control group (6.25% vs. 5.69%, hazard ratio 0.936 [95% confidence interval 0.904-0.970], p < 0.001*). By site, hip fractures significantly decreased (0.89% vs. 0.42%, p < 0.001), but not vertebral and radial fractures. Subgroup analysis by vitamin D type showed a significantly lower incidence of total fractures only in alfacalcidol (hazard ratio 0.676 [95% confidence interval 0.628-0.728], p < 0.001*). The results suggest that vitamin D prescription was associated with a reduced incidence of hip fractures.

Association between trunk-to-peripheral fat ratio and renal function in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS: Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION: Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.

Relationship between antidementia medication and fracture prevention in patients with Alzheimer's dementia using a nationwide health insurance claims database.

This retrospective study aimed to evaluate the association between antidementia medication use and incidence of new vertebral, hip, and radial fractures in patients with Alzheimer's dementia (AD). We used the nationwide health insurance claims database of Japan from 2012 to 2019 and identified 12,167,938 patients aged ≥ 65 years who were newly registered from April 2012 to March 2016 and had verifiable data receipt from half-year before to 3 years after the registration. Among these patients, 304,658 were diagnosed with AD and we showed the prescription status of antidementia and osteoporosis medication among them. Propensity score matching was conducted for AD group with and without antidementia medication use, and 122,399 matched pairs were yielded. The incidence of hip fractures (4.0% vs. 1.9%, p < 0.001) and all clinical fractures (10.5% vs. 9.0%, p < 0.001) significantly decreased and that of radial fractures increased (0.6% vs. 1.0%, p < 0.001) in AD patients with antidementia medication use compared with AD patients without antidementia medication use. No significant difference was found in vertebral fractures (6.6% vs. 6.5%, p = 0.51). Overall, these results suggest a positive relationship between antidementia medication use and fracture prevention in patients with AD.

Association between pharmacotherapy and secondary hip fracture in a real-world setting: a nationwide database study.

INTRODUCTION: This study aimed to assess the association between pharmacotherapy and secondary hip fracture incidence. MATERIALS AND METHODS: The correlation between secondary hip fracture incidence and the presence, type, and medication possession ratio (MPR) of pharmacotherapy was investigated using medical insurance data acquired from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. RESULTS: Data collected from female patients (n = 1,435,347) were analyzed. The 2-year secondary hip fracture incidence was 3.48% (n = 49,921). Secondary hip fracture was significantly more common in patients without medications (3.80%) than in those with medications (3.00%). Patients receiving selective estrogen receptor modulators (SERMs) had the lowest average age. The crude incidence of secondary hip fracture was the lowest in patients receiving SERMs (n = 2088 [2.52%]), followed by those taking bisphosphonates (n = 11,355 [2.88%]), denosumab (n = 1118 [2.90%]), no medications (n = 32,747 [3.80%]), and parathyroid hormone (PTH: n = 2163 [4.55%]), whereas the age-adjusted incidence was the lowest in patients administered denosumab (2.27%), followed by those taking bisphosphonates (2.47%), SERMs (2.55%), PTH (3.67%), and no medications (3.80%). The mean MPR was the highest in patients taking denosumab (64.9%), followed by those receiving bisphosphonates (58.7%), SERMs (58.2%), and PTH (40.6%) in the no hip fracture group. CONCLUSION: Secondary hip fractures were less likely to occur with medication versus no medication. Differences in the crude incidence of secondary hip fracture based on medications usage might be attributed to background characteristics.

Low plasma 25-hydroxyvitamin D levels are associated with an increased risk of depressive symptoms in community-dwelling Japanese people aged between 40 and 74 years: The Murakami cohort study.

BACKGROUND: Association between vitamin D levels and the occurrence of depression are not always consistent. The present cohort study aimed to determine this association in older adults, using a method for measuring vitamin D levels which is more accurate than those used in previous studies. METHODS: Participants were 3447 individuals aged 40-74 years without depressive symptoms at baseline who participated in the 5-year follow-up survey. The baseline investigation, including a self-administered questionnaire survey and blood collection, was conducted in 2011-2013. Plasma 25-hydroxyvitamin D (25[OH]D) levels were measured, and divided into overall quartiles summed up by sub-quartiles and stratified by age, sex, and season. The outcome was depressive symptoms determined by the CES-D (11-item, cut-off score of 6/7) 5 years later. Covariates were demographics, lifestyles, baseline CES-D score, and disease history. RESULTS: Mean plasma 25(OH)D levels were 58.0 nmol/L in men and 45.7 in women (P < 0.0001), and cumulative incidences of depressive symptoms were 249/1577 (15.8 %) in men and 313/1870 (16.7 %) in women (P = 0.4526). The lower 25(OH)D quartile group had higher adjusted ORs in men and women combined (P for trend = 0.0107) and women (P for trend = 0.0003), but not in men. Adjusted ORs of the lowest quartile group were significantly higher than the highest group in men and women combined (OR = 1.39, 95 % CI: 1.06-1.81) and women (OR = 1.89, 95 % CI: 1.31-2.72). LIMITATION: Depressive symptoms were self-reported. CONCLUSIONS: Low vitamin D levels were associated with a high risk of depressive symptoms, especially in women. Women are thus considered a major target for preventing vitamin D deficiency to address depression.

Hip and vertebral fracture risk after initiating antidiabetic drugs in Japanese elderly: a nationwide study.

INTRODUCTION: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ). MATERIALS AND METHODS: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs. RESULTS: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively. CONCLUSIONS: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.

Real-world effectiveness of anti-osteoporosis medications for the prevention of incident hip and clinical vertebral fractures in patients on long-term glucocorticoid therapy: A nationwide health insurance claims database study in Japan.

PURPOSE: Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to clarify the real-world effectiveness of AOMs against incident hip and vertebral fractures in patients undergoing GC therapy using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed up regarding AOM prescription and hip and clinical vertebral fracture incidences for the subsequent 1080 days between 2012 and 2018 were selected from NDBJ. Associations of AOMs prescribed within 90 days since GC therapy initiation with hip or vertebral fracture risk were evaluated by Cox proportional hazards regression using propensity score inverse probability weighting (IPW) for receiving any AOM or individual AOMs. RESULTS: In total, 96,475 women and 98,385 men were included in the analysis; 38.0 % of women and 27.6 % of men received AOMs. Patients who received any AOM and those who received bisphosphonates or denosumab had a significantly lower risk of hip and clinical vertebral fractures than those who received no AOM in both sexes after propensity score IPW. Teriparatide was associated with an increased risk of both fractures in women and an increased risk of clinical vertebral fractures in men. Selection biases such as confounding by indication might have caused an underestimation of AOMs' protective effects. CONCLUSIONS: Bisphosphonates and denosumab were associated with a lower fracture incidence in patients on long-term GC therapy in real-world settings.

Breakfast Skipping and Declines in Cognitive Score Among Community-Dwelling Older Adults: A Longitudinal Study of the HEIJO-KYO Cohort.

Previous studies outlined the correlation of adverse effects of breakfast skipping with cognitive function. However, the majority of these studies have focused on the short-term effects; to date, the long-term effect of breakfast skipping on cognitive function among older adults remains unclear. In this prospective cohort study of 712 older adults (mean age, 70.8 years), breakfast skipping was defined as skipping breakfast one or more times per week, and declines in cognitive score was defined as decreases in Mini-Mental State Examination (MMSE) score of two or more in the observed period. During follow-up (median, 31 months), 135 of 712 participants developed declines in cognitive score. Poisson regression models revealed that the incidence rate for declines in cognitive score was significantly higher in breakfast skipper (n = 29) than breakfast eaters (n = 683) [incidence rate ratio (IRR), 2.10; 95% CI, 1.28-3.44]. Additional propensity score adjustments related to breakfast skipping from baseline parameters (age, gender, smoking and drinking status, BMI, household income, educated level, depressive symptoms, hypertension, diabetes, sleep medication, physical activity, caloric intake, and baseline cognition) produced consistent results (IRR, 2.21; 95% CI, 1.33-3.68). Sensitivity analysis, when the cut-off value of decreases in MMSE score was changed to three points, suggested a significant and stronger association (IRR, 3.03; 95% CI, 1.72-5.35). Regarding daily intakes of food groups, breakfast skippers consumed a significantly lower amount of vegetables, fruits, and fish than breakfast eaters. In conclusion, our findings suggest that breakfast skipping is longitudinally associated with declines in cognitive score among older adults.

Physical activity and recurrent fall risk in community-dwelling Japanese people aged 40-74 years: the Murakami cohort study.

BACKGROUND: Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people. METHODS: This cohort study targeted 7,561 community-dwelling individuals aged 40-74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls. RESULTS: Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33-2.88] and 2.15 [95%CI:1.48-3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49-0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29-0.85]) but not in men. CONCLUSIONS: Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.

Association of pharmacotherapy with the second hip fracture incidence in women: A retrospective analysis of the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

AIM: Second hip fractures worsen the quality of life and are associated with increased mortality. We clarified the association between the pharmacotherapy and second hip fracture prevention. METHODS: The relationship between the incidence of second hip fracture and the presence, type and medication possession ratio (MPR) of pharmacotherapy was investigated using medical insurance data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan during April 2012 to March 2019. RESULTS: Data of 776 040 female patients were analyzed. The 2-year rate of second hip fractures was 3.31% (n = 25 684). Bisphosphonates (n = 148 138, 19.1%) were the most commonly used medications after primary hip fracture. Patients receiving selective estrogen receptor modulators (SERMs) had the lowest age, followed by those receiving bisphosphonates, denosumab and parathyroid hormone (PTH). The second hip fracture crude incidence was lowest in patients administered SERMs (n = 859, 2.44%), followed by those administered bisphosphonates (n = 4451, 3.00%), denosumab (n = 484, 3.19%), no medication (n = 19 017, 3.39%) and PTH (n = 873, 5.35%); however, the age-adjusted incidence was the lowest in patients administered denosumab (2.22%), followed by those administered bisphosphonates (2.35%), SERMs (2.39%), no medications (3.39%) and PTH (3.67%). The MPR was highest in patients administered denosumab (60.0%). Among patients without a second hip fracture, the rate of patients with MPR ≥80% was highest among those administered SERMs (40.8%), followed by those administered bisphosphonates (38.0%), denosumab (35.4%) and PTH (12.2%). CONCLUSION: Differences in patient background characteristics and the rate of patients with MPR ≥80% might underlie the observed differences in the crude incidence of second hip fracture among the medication groups. Geriatr Gerontol Int 2022; 22: 930-937.

Risk factors for future osteoporosis in perimenopausal Japanese women.

OBJECTIVE: The aims of this study were to investigate trends in bone mineral density (BMD) loss and related factors in early postmenopausal women in Japan, identify risk factors for future osteoporosis, and predict osteoporosis before it occurs. METHODS: The study population consisted of women who were 50 to 54 years old at the time of the survey in 2002 or 2006. The study included a questionnaire and physical measurement findings (BMD, height, body weight [WT], body mass index [BMI], and handgrip strength). One hundred sixty-seven women continued to participate in the study and had BMD measurements at the 9- or 10-year follow-up of the Japanese Population-based Osteoporosis study. Statistical analyses were performed using Pearson correlation to examine each factor of physical measurement and BMD for lumbar spine (LS) and femoral neck (FN). The receiver operating characteristic curve of this data was also predictive of osteoporosis in 2011 for 2002 data; BMD at the age of 50 to 54 years was then used to predict the likelihood of being diagnosed with osteoporosis 9 and 10 years later. RESULTS: At the baseline in 2002 and 2006, WT, BMI, height, and handgrip strength were positively correlated with BMD. The optimal cutoff values for BMD in 2006 to predict osteoporosis in 2016 were LS less than 0.834 g/cm 2 and FN less than 0.702 g/cm 2 . These data were also predictive of osteoporosis in 2011 for 2002 data; applying this to the 2002 data, LS/FN had a sensitivity of 92%/100%, a specificity of 87%/81%, a positive predictive value of 55%/48%, and a negative predictive value of 98%/100%. The larger WT and BMI also resulted in a greater decrease in BMD of FN after 9 or 10 years. CONCLUSIONS: We have identified a cutoff value for BMD to predict future osteoporosis in menopausal women and found a negative correlation between WT and BMI in menopausal women and changes in BMD of the FN over the next 10 years.

Body weight at 1.5- and 3-year health checks and body fat at 14 years of age: a population-based retrospective cohort study using dual-energy X-ray absorptiometry.

BACKGROUND: In Japan, height and weight measurements, taken for all children at birth and 1.5- and 3-year health checks, are recorded in the Mother and Child Health (MCH) Handbook, as required by the law. The present population-based retrospective cohort study aimed to evaluate the diagnostic performance of height and weight records in the Handbook for predicting excessive adiposity in adolescents. METHODS: The source population consisted of 8th grade students (800 students aged 14 years) registered at two public junior high schools. Of these, we excluded students who were born at a gestational age < 37 weeks or > 42 weeks. The present analyses included 435 participants who provided complete information. Body mass index (BMI) was calculated using height and weight records. Body fat mass at 14 years of age was measured by dual-energy X-ray absorptiometry (DXA). Diagnostic performance of BMI calculated from the MCH Handbook records to discriminate between the presence and absence of excessive adiposity at 14 years of age was evaluated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of BMI. RESULTS: With regard to the prediction of excessive fat at 14 years of age, AUCs and 95% confidence intervals for BMI at 1.5 and 3 years of age were greater than 0.5. Meanwhile, the AUC of BMI at birth was not significantly greater than 0.5. CONCLUSION: The present study findings indicate that BMI values calculated using MCH Handbook data have potential ability to distinguish between the presence and absence of excessive fat at 14 years of age.

Delayed initiation of anti-osteoporosis medications increases subsequent hip and vertebral fractures in patients on long-term glucocorticoid therapy: A nationwide health insurance claims database study in Japan.

PURPOSE: Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to examine whether physicians prescribe AOMs as soon as GC therapy is initiated, and whether a delay in AOM initiation affects hip and vertebral fracture incidence, using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed for AOM use and hip and vertebral fracture events for the subsequent 1080 days in 2012-2018 were selected from NDBJ. Delay in AOM initiation was defined as the number of days without AOMs following GC therapy initiation. Associations between delay in AOM initiation and hip and vertebral fracture risk were evaluated by Cox proportional hazards regression. RESULTS: In total, 92,143 women and 94,772 men were included in the analysis, of which only 39.3% of women and 28.5% of men received AOMs within 90 days from GC therapy initiation. Approximately, 15% of hip fractures and 30% of vertebral fractures occurred before AOM initiation in patients with delayed AOM initiation. HRs of both fractures were significantly greater in patients with a longer delay in AOM initiation (p value for trend<0.001). After excluding patients who had fractures before AOM initiation, the magnitude of HRs significantly decreased, and HR trends for hip fracture became insignificant. CONCLUSIONS: Delayed initiation of AOMs may result in increased fracture events, which may be reduced by early initiation of AOMs.

Leisure-Time and Non-Leisure-Time Physical Activities are Dose-Dependently Associated With a Reduced Risk of Dementia in Community-Dwelling People Aged 40-74 Years: The Murakami Cohort Study.

OBJECTIVE: Although physical activity (PA) in late life is considered a preventive factor for dementia, effects of different types of PAs on the development of dementia in early old age are unclear. This study aimed to determine the effect of leisure-time and non-leisure-time PAs on dementia risk in middle-aged and older adults during an 8-year follow-up. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Participants were 13,773 community-dwelling individuals aged 40-74 years who completed the baseline self-administered questionnaire survey of the Murakami cohort study in 2011-2013. METHODS: Main predictors were leisure-time and non-leisure-time (commute, occupational work, and housework) PAs as assessed by MET score (MET-hour/d). The outcome was newly developed dementia determined using a long-term care insurance database. Covariates included demographics, lifestyle, body size, disease history, and PA level. Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: Mean age of participants was 59.0 (SD 9.3) years. Higher levels of leisure-time PA were associated with lower HRs (adjusted P for trend <.001), with all tertiles having significantly lower HRs (low: 0.71, 95% CI 0.51-0.99; medium: 0.59, 95% CI 0.43-0.81; high: 0.55, 95% CI 0.41-0.75) relative to the reference (zero). Higher quartiles of non-leisure-time PA were associated with lower adjusted HRs for dementia (adjusted P for trend < .001), with the second-fourth quartiles having significantly lower HRs (second: 0.73, 95% CI 0.54-0.98; third: 0.59, 95% CI 0.43-0.81; fourth: 0.55, 95% CI 0.41-0.75) relative to the lowest quartile. These associations were robust regardless of sex and age group. CONCLUSIONS AND IMPLICATIONS: Both leisure-time and non-leisure-time PAs are independently and robustly associated with a reduced risk of dementia.