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.

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.

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.

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.

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.

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.

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.

Insufficient persistence to pharmacotherapy in Japanese patients with osteoporosis: an analysis of the National Database of Health Insurance Claims and Specific Health Checkups in Japan.

In Japan, persistence and the 2-year MPR were inadequate in increasing fracture control efficacy despite a high adherence rate during the treatment period. Both factors were higher in females and those with polypharmacy but worsened with increasing age. PURPOSE: Only a few large-scale studies have examined the care gap between the patients who need osteoporosis treatment and those who receive them in Japan. The aim of this study was to investigate the persistence and adherence to osteoporosis pharmacotherapy in Japan. METHODS: Continuation (persistence) rates and adherence to osteoporosis pharmacotherapy were investigated using medical insurance data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, between April 2012 and March 2019. RESULTS: The study included 528,806 male and 3,064,410 female patients. Persistence proportions were 56.6% in the first year and 46.3% in the second year. The medication possession ratio (MPR) from start to discontinuation of treatment (MPRdiscon) was 94.5%, and 92.7% of patients had an MPRdiscon ≥ 80%. The 2-year MPR (MPR730) was 61.9%, and 49.6% of patients had an MPR730 ≥ 80%. Both the persistence proportion and MPR730 were higher in females than in males, whereas MPRdiscon was higher in males. The persistence proportion and MPR730 were highest in the 70-79 years age group, whereas MPRdiscon improved with increasing age. The MPRdiscon and MPR730 were higher in the mixed-fracture and vertebral-fracture groups, respectively. The persistence proportion, MPRdiscon, and MPR730 were higher in patients with polypharmacy than in those without. CONCLUSION: In Japan, persistence and the 2-year MPR were inadequate in increasing fracture control efficacy despite a high adherence rate during the treatment period. To bridge the care gap following osteoporosis pharmacotherapy, improvements are required for males, the elderly, and those without polypharmacy.

Insufficient increase in bone mineral density testing rates and pharmacotherapy after hip and vertebral fracture: analysis of the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

Test and treatment rates for osteoporosis in Japan aimed at preventing secondary fragility fractures were insufficient. Those who suffered hip fractures had approximately half the rates of those who suffered vertebral fractures, with such rates being lower among those over 80 years old and males. PURPOSE: The present study aimed to examine the care gap for secondary fracture prevention in Japan given the few large-scale studies regarding the matter. METHODS: Changes in bone mineral density testing (test rate) and osteoporosis pharmacotherapy administration (treatment rate) rates before and after hip and vertebral fracture registration were examined using medical insurance data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan issued from April 2012 to March 2019. RESULTS: The hip fracture group comprised 677,480 women and 264,003 men, the vertebral fracture group comprised 703,247 women and 251,542 men, and the mixed fracture group comprised 3614 women and 1055 men. Test rates were 14.1%, 25.3%, and 17.6% prior to fracture registration (pre-registration) and 22.3%, 43.6%, and 28.1% after fracture registration (post-registration) in the hip, vertebral, and mixed fracture groups, respectively. Moreover, pre-registration treatment rates were 21.2%, 33.5%, and 30.7%, while post-registration rates were 31.6%, 61.7%, and 46.6% in the hip, vertebral, and mixed fracture groups, respectively. All fracture groups showed a tendency for decreased post-registration test and treatment rates among those aged over 80 years old, with men having lower rates. Moreover, 184,180 (19.4% of whom received new treatment) and 707,263 (23.8% of whom received new treatment) patients with and without polypharmacy underwent treatment after registration, respectively. CONCLUSION: To bridge the care gap following fractures, medical professionals should change their perception regarding osteoporosis treatment in patients with hip fractures, elderly individuals undergoing polypharmacy, and males.

Insufficient persistence of and adherence to osteoporosis pharmacotherapy in Japan.

INTRODUCTION: Only a few large-scale studies have examined the care gap in Japan. The aim of this study was to investigate the persistence of and adherence to osteoporosis pharmacotherapy in Japan. MATERIALS AND METHODS: The rates of continuation (persistence) of and adherence to osteoporosis pharmacotherapy were investigated using medical insurance data, issued from July 2013 to December 2018, from the medical care system for elderly individuals in Hokkaido, Japan. RESULTS: The study included 7918 male and 52,585 female patients. Persistence rates were 62.1% in the first year and 45.3% in the second year. There were 33,096 patients who discontinued medication; 8296 patients resumed medication during the observation period of 730 days. The median time to the discontinuation of medication for all the patients was 702 days. The 2-year medication possession ratio (MPR) was 63.8%; 30,989 patients (51.2%) had an MPR ≥ 80% and 20,788 (34.4%) had an MPR < 50%. Both the persistence and adherence were better in females than in males and worsened with increasing age. Comparisons of fracture history showed that persistence and MPR were higher in the no hip or vertebral fracture group, followed by hip fracture, vertebral fracture, and hip and vertebral fracture groups. Meanwhile, more patients in the hip fracture group had an MPR ≥ 80%. CONCLUSION: Persistence of and adherence to osteoporotic pharmacotherapy are not very high in Japan. To bridge the care gap following osteoporosis pharmacotherapy, improvements are required for males, the elderly, and those with a history of vertebral fracture.

Insufficient increase in bone mineral density testing rates and pharmacotherapy after hip fracture in Japan.

INTRODUCTION: Only a few large-scale studies have examined the care gap in Japan. The present study aims to examine the care gap for secondary fracture prevention. MATERIALS AND METHODS: Changes in the rates of bone mineral density testing (test rate) and osteoporosis pharmacotherapy administration (treatment rate) before and after hip and vertebral fracture registration were examined based on medical insurance data from the medical care system for elderly individuals in Hokkaido, Japan, issued from July 2013 to December 2018. RESULTS: The hip fracture group comprised 18,258 women and 4162 men, whereas the vertebral fracture group comprised 34,907 women and 9958 men. Test rates were 0.2% and 1.4% prior to fracture registration (pre-registration) and 19.9% and 40.5% after fracture registration (post-registration) in the hip and vertebral fracture groups, respectively. Moreover, pre-registration treatment rates were 18.3% and 28.2% and post-registration rates were 32.7% and 61.0% in the hip and vertebral fracture groups, respectively. The vertebral fracture group had a significantly higher post-registration test and treatment rates than the hip fracture group. Moreover, the post-registration test and treatment rates in the hip fracture group tended to increase over the years. Both fracture groups showed a tendency for decreased post-registration test and treatment rates as age increased, with lower rates observed among men. CONCLUSIONS: Test and treatment rates after hip fracture registration remain lower compared with those after vertebral fracture registration. To bridge the care gap following fractures, medical professionals need better awareness regarding osteoporosis treatment for hip fractures among elderly individuals and males.

Relationships between chronic pain with locomotive syndrome and somatic symptom disorder in general community-dwelling population: A cross-sectional evaluation of individuals aged 50 years or older undergoing primary specific health screening.

Objectives: We aimed to determine the prevalence of chronic pain and its relationship with locomotive syndrome (LS) and somatic symptom disorder.Methods: A cross-sectional survey to assess factors associated with poor prognosis of chronic pain in individuals aged 50 years or older presenting for annual health checkups in Asahimachi, Japan in 2017. The Michigan Body Map, Loco-check and Somatic Symptom Scale-8 (SSS-8) were used to assess chronic pain, LS, and somatic symptom disorder, respectively.Results: Of 1678 individuals assessed, 57% had chronic pain; 57% and 71% were positive for Loco-check and SSS-8, respectively. Chronic pain prevalence was higher among Loco-check-positive individuals (OR, 2.823; 95% CI, 2.278-3.499) and among SSS-8-positive individuals (OR, 15.199; 95% CI, 11.194-20.636). Loco-check-positive individuals had significantly more pain sites than Loco-check-negative individuals. A significant correlation was found between SSS-8 scores and the number of pain sites.Conclusion: A high proportion of community-dwelling individuals aged 50 years or older had multiple pain sites and concurrent chronic pain, LS, and somatic symptom disorders. The number of pain sites correlated with LS and somatic symptom disorder. Thus, evaluating these could help physicians to take into account how chronic pain affects patients in terms of functional and psychological aspects.

Screening program including the Loco-check and fracture risk assessment tool (FRAX®) questionnaires for assessing locomotive syndrome in a municipality in Japan: A pilot study.

BACKGROUND: Although the concept of locomotive syndrome and its relevant test methods have been established, approaches for incorporating them into regular health checkups have not been established. We aimed to assess the utility and problems of including Loco-check and the fracture risk assessment tool (FRAX®) as primary screening for locomotive syndrome during health checkups under the Act on Assurance of Medical Care for Elderly People (specified health checkup) in the municipality. METHODS: Loco-check and FRAX® questionnaires were mailed to subjects eligible for the 2015 specified health checkup in Asahi-machi, Japan. Subjects with more than one affirmative response in the Loco-check questionnaire (Loco-check positive) or whose FRAX® major osteoporotic fracture risk was ≥10% (FRAX® positive) were identified as high risk and were evaluated in secondary checkups that included an locomotive syndrome risk test and sarcopenia and bone mineral density screenings. The degree of locomotive syndrome was assessed according to clinical diagnostic criteria of the Japanese Orthopaedic Association. RESULTS: Questionnaires were collected from 2209 subjects and included 1193 Loco-check-positive and 1108 FRAX®-positive subjects. There were 367 FRAX®-positive subjects who were Loco-check-negative and 452 Loco-check-positive subjects who were FRAX®-negative. Three hundred fifty-one subjects completed secondary checkups (42 in the no locomotive syndrome group, 171 in the locomo stage 1 group, and 138 in the locomo stage 2 group). Fourteen subjects had sarcopenia. CONCLUSION: The locomotive syndrome prevalence is high among subjects eligible for specified health checkups; these subjects were appropriate for locomotive syndrome screening. Using Loco-check and FRAX® in primary screening, many subjects can be evaluated for locomotive syndrome in a timely and cost-effective manner, a more diversified risk of fall/fracture can be obtained, and the sensitivity of screening may be increased. These checkup protocols will assist in promoting locomotive syndrome checkups in municipalities throughout Japan.

Effect of osteoporosis medication on changes in bone mineral density and bone turnover markers after 24-month administration of daily teriparatide: comparison among minodronate, raloxifene, and eldecalcitol.

This study reveals the changes in bone mineral density (BMD), the turnover rate, and the balance [multiple of median formation/multiple of median resorption (MoMf/MoMr)] affected by the selection of different bone resorption inhibitors after 24-month daily teriparatide (20 µg/day) administration. The turnover rate was calculated as √(MoMf2 + MoMr2), where MoMf = bone-specific alkaline phosphatase (BAP) value/18.6 and MoMr = tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463. One hundred and twenty-one osteoporotic women (mean age 82.4 years) were randomly administered minodronate (50 mg/28 days), raloxifene (60 mg/day), or eldecalcitol (0.75 µg/day) after teriparatide discontinuation. BMD was measured at 0, 24, and 48 weeks; BAP values and TRACP-5b were measured at 0, 12, 24, 36, and 48 weeks after administration of bone resorption inhibitors. In the minodronate group, BMD increased significantly from week 0 to weeks 24 and 48. The turnover rate was significantly reduced at week 12, and remained so over the entire course in all three groups. The speed of change of turnover rate was greatest in the minodronate group. The balance in the minodronate group shifted significantly toward formation dominance at week 12 (to 0.97 from 0.87) and then again toward resorption dominance (to 0.84) at week 24. However, no further advancement in resorption dominance was observed until week 48. Conversely, the balance in the raloxifene and eldecalcitol groups shifted toward resorption dominance gradually over the entire course. In conclusion, the BMD-increasing effect was greatest with minodronate administration and depends not only on the decrease in turnover rate but also on changes in balance after teriparatide discontinuation.

[Primary fracture prevention through the Osteoporosis Liaison Service.]

It is difficult to prevent primary fragility fractures because the subjects have not yet experienced a fracture. The offers of the community Osteoporosis Liaison Service are important for primary prevention of fragility fractures. The prevention, education, enlightenment, and the offer of osteoporosis examinations are included in this service. It is necessary to deliver the prevention services and osteoporosis education according to the age of the subjects. Hence, for young people, it is effective to include in school education that getting high peak bone mass is important, and for the middle-aged population, it is necessary to include education on the maintenance of bone quantity and the impact on risk factors such as smoking and excessive alcohol consumption. Furthermore, early detection of osteoporosis is important, with an osteoporosis check-up being one of the few opportunities for assessing the bone mineral density(BMD)in elderly women. However, there are some problems with osteoporosis check-ups in Japan. First, the implementation and participation rates of osteoporosis check-ups are low. Second, only BMD is set as the most important value for the assessment. Third, the subjects are limited to women in the range of 40-70 years of age with the knot age set at every 5 years. Finally, the setting of the BMD measuring apparatus is low. We adopted Fracture Risk Assessment Tool(FRAX)and loco-check for check-ups at Asahi-machi in the Toyama Prefecture to resolve the above problems and have reported its usefulness. Action by the Osteoporosis Liaison Service to enforce osteoporosis check-ups is expected. Various types of professional medical staff participate in the Osteoporosis Liaison Service as osteoporosis managers. It is desired that the managers will cooperate and function as an osteoporosis project team in the community.

Bone turnover rate and bone formation/resorption balance during the early stage after switching from a bone resorption inhibitor to denosumab are predictive factors of bone mineral density change.

OBJECTIVES: This study aimed to investigate the correlation between bone mineral density (BMD) and the turnover rate [√(MoMf2 + MoMr2), multiple of median formation (MoMf) was calculated as bone-specific alkaline phosphatase (BAP) value/18.6 and multiple of median resorption (MoMr) as tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463] and the balance (MoMf/MoMr) and to compare differences in therapeutic effects evoked by differences in previous treatments. METHODS: In 51 osteoporotic women treated with bisphosphonates (BPs) or selective estrogen receptor modulators (SERMs), BMD was measured at 0, 24, and 48 weeks after denosumab administration. The values of BAP and TRACP-5b were measured at 0, 4, 12, 24, 36, and 48 weeks. RESULTS: The turnover rate decreased at week 4 and decreased further at week 12. The balance indicated a relative predominantly formative state at week 4. This balance became higher in the SERM group than in the BP group at week 4. A correlation was observed between the rate of BMD change and turnover rate at weeks 0 and 4. CONCLUSIONS: It is necessary to evaluate the turnover rate and balance to determine the therapeutic effect of denosumab, which induces dissociation between the trends in the bone turnover markers. Turnover rate and balance during the early stages of denosumab treatment may be predictive factors of BMD. When switching from bone resorption inhibitors to denosumab, it was necessary to consider the beginning values that were affected by the previous treatment. The state of relative anabolism is greater at 4 weeks when the previous treatment involved SERMs rather than BPs.

The importance of assessing the rate of bone turnover and the balance between bone formation and bone resorption during daily teriparatide administration for osteoporosis: a pilot study.

This study aimed to examine the importance of simultaneously measuring bone formation and resorption markers during daily teriparatide administration. In 135 women with osteoporosis, bone mineral density (BMD) was measured at 0, 24, and 48 weeks after teriparatide administration. Bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b were measured at 0, 4, 12, 24, 36, and 48 weeks. Subanalyses were performed in groups divided according to the BMD change at 48 weeks (increased and decreased groups), history of fragility fracture (acute and chronic groups), and treatment prior to teriparatide administration (alendronate, raloxifene, and naïve groups). The scatter diagram of multiple of median formation (MoMf) and multiple of median resorption (MoMr) showed that the distribution gradually spread to a high turnover by week 24. A significant correlation was observed between the rate of change in BMD at week 48 and the turnover rate [√(MoMf(2) + MoMr(2))] at week 0. Significant differences were observed in the turnover rate between the acute and chronic groups at weeks 0 and 4 and between the groups divided according to prior treatment from week 0 to 24. Because the assessment of either bone formation markers or bone resorption markers may result in erroneous data, it is necessary to assess them together during teriparatide treatment. The turnover rate at treatment initiation is a useful indicator to predict changes in BMD. When evaluating the turnover rate and balance (MoMf/MoMr), one should consider patient characteristics, including history of fragility fracture and prior treatment.