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.

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.

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.