Bonanni R, Falvino A, Smakaj A
… +7 more, Tranquillo L, Rinaldi AM, D'Arcangelo G, Cifelli P, Tancredi V, Cariati I, Tarantino U
J Bone Miner Metab
· 2025 Nov · PMID 40956314
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INTRODUCTION: Osteoarthritis and osteoporosis are age-related musculoskeletal disorders characterized by increased oxidative stress and cellular senescence, which contribute to altered metabolism and disease progression....INTRODUCTION: Osteoarthritis and osteoporosis are age-related musculoskeletal disorders characterized by increased oxidative stress and cellular senescence, which contribute to altered metabolism and disease progression. Although research in this field is constantly evolving, the discovery of new molecular targets and drug combinations to counteract musculoskeletal disorders remains a goal of great interest. This study aimed to evaluate the efficacy of a cocktail of trolox, recombinant irisin (r-irisin) and resveratrol in modulation of osteoblastic metabolism by investigating the expression of NADPH oxidase 4 (NOX4), sirtuin 1 (SIRT1) and pentraxin 3 (PTX3). MATERIALS AND METHODS: 20 male patients undergoing hip arthroplasty were enrolled, including ten patients with coxarthrosis and ten patients with osteoporosis. Femoral head biopsies were taken from each patient to isolate primary osteoblast cultures, which were treated with the cocktail for 6 days. RESULTS: The cocktail of trolox, r-irisin and resveratrol increased cell viability, and reduced ROS and senescence β-galactosidase activity (SA-β-Gal) levels. In addition, western blotting analysis showed reduced expression of NOX4 and increased expression of SIRT1 and PTX3 in both experimental groups, although with more pronounced effects in osteoarthritic patients, highlighting lower treatment efficacy in the presence of osteoporosis. CONCLUSIONS: The improvement in cell viability and reduction in oxidative stress and cellular senescence observed through treatment-induced modulation of the NOX4-SIRT1 axis and PTX3 suggests a protective role for these biomarkers in bone metabolism. These findings could offer new perspectives in counteracting the effects of aging on the skeletal system by improving bone health and mitigating metabolic alterations.
Tanaka S, Uemura Y, Tanaka S
… +7 more, Takeuchi Y, Endo N, Takada J, Ikeda S, Iwamoto J, Okimoto N, Soen S
J Bone Miner Metab
· 2025 Nov · PMID 40900219
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INTRODUCTION: Although bone anabolic agents such as teriparatide are effective for osteoporosis, satisfaction and adherence may vary by regimen. This multicenter study assessed long-term satisfaction, persistence, effica...INTRODUCTION: Although bone anabolic agents such as teriparatide are effective for osteoporosis, satisfaction and adherence may vary by regimen. This multicenter study assessed long-term satisfaction, persistence, efficacy, and safety in postmenopausal women with primary osteoporosis treated with alternating daily and twice-weekly teriparatide over 52 weeks, followed by a final free-choice treatment period. MATERIALS AND METHODS: In a randomized, open-label, crossover study, 358 postmenopausal women at high risk for fracture were assigned to receive once-daily (20 µg) or twice-weekly (28.2 µg) subcutaneous teriparatide for 26 weeks, then crossed over to the alternative regimen for another 26 weeks. Afterwards, 233 patients entered a 52-week free-choice period under their preferred regimen. RESULTS: Among the 233 patients entering the free-choice period, 162 chose twice-weekly and 71 chose daily teriparatide. Persistence at 104 weeks was 90.1% for twice-weekly and 88.7% for daily groups (p = 0.749). Overall and treatment satisfaction between groups did not differ significantly at 104 weeks (p > 0.05). Fracture incidence was low and similar (2.8% vs. 1.2%, p = 0.758). Patients in both groups showed significant increases in bone mineral density at L2-L4 and the femoral neck (p < 0.05). Adverse events were infrequent and non-severe. CONCLUSIONS: Patient satisfaction and efficacy were maintained with both teriparatide regimens over 104 weeks, and persistence improved during the patient-choice phase. Supporting patient preference may improve adherence to osteoporosis medications. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials ID: jRCTs031210187.
INTRODUCTION: Hyperglycemia increases the risk of bone fragility by promoting reactive oxygen species and advanced glycation end products, which disrupt osteoblast activity. Mechanical stress, including osmotic stress fr...INTRODUCTION: Hyperglycemia increases the risk of bone fragility by promoting reactive oxygen species and advanced glycation end products, which disrupt osteoblast activity. Mechanical stress, including osmotic stress from elevated glucose levels, affects bone homeostasis; however, the specific impact of osmotic stress on osteoblast function is not fully understood. The transient receptor potential vanilloid 4 (TRPV4) channel, known to mediate calcium influx in response to mechanical stress, plays a key role in osteoblast differentiation. This study investigated the effects of osmotic stress on osteoblast differentiation and mineralization, as well as the role of TRPV4-mediated calcium influx. MATERIALS AND METHODS: We investigated the effects of osmotic stress on osteoblast differentiation and mineralization using MC3T3-E1 cells. Mannitol and sorbitol treatments were adjusted to match the osmolality of glucose to assess osmotic stress effects. TRPV4 involvement was examined using the TRPV4 antagonist, HC-067047. RESULTS: Mineralization was inhibited not only by glucose, but also by treatment with mannitol and sorbitol, which were adjusted to match the osmolality of glucose. Both glucose and mannitol treatments inhibited the nuclear translocation of Runx2 while decreasing the mRNA expression of osteogenic markers such as osteocalcin, ALP, and collagen I. Notably, osmotic stress suppressed calcium influx through TRPV4 channels, which is linked to differentiation induction. Furthermore, HC-067047 inhibited mineralization and osteogenic marker expression. CONCLUSION: These findings indicate that osmotic stress impairs osteoblast mineralization by inhibiting TRPV4-mediated calcium influx. TRPV4 may represent a therapeutic target for mitigating bone loss in diabetes, suggesting a novel approach for treating diabetic bone disease.
INTRODUCTION: Few studies assessed comprehensive effects of composite unhealthy lifestyles on aging and musculoskeletal health. This study aimed to address such issues with the UK Biobank datasets. MATERIALS AND METHODS:...INTRODUCTION: Few studies assessed comprehensive effects of composite unhealthy lifestyles on aging and musculoskeletal health. This study aimed to address such issues with the UK Biobank datasets. MATERIALS AND METHODS: An unhealthy lifestyle score (UHLS) was constructed based on 9 lifestyle behaviors. Aging indicators were calculated from 18 clinical traits. General linear and Cox proportional hazards regression models were used to analyze associations between UHLS, aging, and musculoskeletal morbidity. Mendelian randomization (MR) analysis was performed for causal relationship exploration. RESULTS: Among 396,037 participants, 54.5% and 3.3% of them were designated to the low (scored 0-2) and high UHLS (scored 6-9) groups, respectively. Increasing UHLS was associated with elevated aging acceleration (AA) based on biological age (0.343 per unit; 95% CI: 0.331, 0.355) and phenotypic age (AA_PA) (0.408 per unit; 95% CI: 0.394, 0.422), and higher morbidity of low grip strength (HR = 1.025; 95% CI: 1.001, 1.050), slow walking pace (HR = 1.134; 95% CI: 1.074, 1.198), osteoporosis (HR = 1.077; 95% CI: 1.063, 1.091), fracture (HR = 1.059; 95% CI: 1.048, 1.069) and osteoarthritis (HR = 1.036; 95% CI: 1.030, 1.042). Unhealthy lifestyles in conjunction with AA jointly increased musculoskeletal morbidity. Besides, AA mediated UHLS effects on slow walking pace, osteoporosis and fracture, with mediating proportion of 4.85%-12.79%. MR analyses revealed causal relationships between UHLS and low grip strength, osteoarthritis, and reduced femoral neck bone mineral density. In addition, AA_PA suggestively mediated the UHLS-osteoarthritis association. CONCLUSIONS: Composite unhealthy lifestyles accelerate aging and impair musculoskeletal health. Both mediating and joint effects of AA showed unhealthy lifestyle-associated musculoskeletal morbidity.
Mori S, Tanaka S, Kuroda T
… +2 more, Hagino H, Soen S
J Bone Miner Metab
· 2025 Sep · PMID 40745050
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INTRODUCTION: The effects of teriparatide (TPTD) and alendronate (ALN) on health-related quality of life (HRQOL) were evaluated in osteoporotic patients with high fracture risk using data from the JOINT-05 trial. MATERIA...INTRODUCTION: The effects of teriparatide (TPTD) and alendronate (ALN) on health-related quality of life (HRQOL) were evaluated in osteoporotic patients with high fracture risk using data from the JOINT-05 trial. MATERIALS AND METHODS: JOINT-05 was a randomized, controlled trial comparing the fracture prevention effects of sequential therapy with TPTD for 72 weeks followed by ALN for 48 weeks with those of ALN monotherapy for 120 weeks. This sub-analysis evaluated the effects of TPTD and ALN on HRQOL using data from baseline to 72 weeks. HRQOL was assessed at baseline, 4, 12, 24, 48, and 72 weeks using the EuroQoL-5Dimension (EQ-5D) questionnaire containing five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Scores were also transformed using utility weights derived from the general Japanese population. RESULTS: This sub-analysis included 476 patients in the TPTD group and 492 patients in the ALN group. No significant differences in utility scores were observed between groups at all times. Utility scores improved significantly after 12 weeks in the TPTD group and after 24 weeks in the ALN group. Mobility and self-care scores improved significantly in the TPTD group. Significant improvements in usual activity, pain/discomfort, and anxiety/depression scores occurred earlier in the TPTD group. CONCLUSION: Although there were no significant differences in utility scores between the TPTD and ALN groups, significant improvements in the utility score and 5 domain scores were observed earlier in the TPTD group. When treating osteoporosis patients with a high risk of fracture, the selecting treatment drugs may be decided with primary consideration of its effect on fracture prevention, followed by its effect on improving HRQOL.
INTRODUCTION: Hip fracture (HF) is one of the leading causes of mortality and disability in older populations. Hip refracture (HRF) is more serious than HF. We examined the survival rates of patients with HRFs at the Aff...INTRODUCTION: Hip fracture (HF) is one of the leading causes of mortality and disability in older populations. Hip refracture (HRF) is more serious than HF. We examined the survival rates of patients with HRFs at the Affiliated Dongyang Hospital of Wenzhou Medical University and developed a prediction model for their survival outcomes. MATERIALS AND METHODS: This study involved identifying and analyzing patients with HRFs from January 2013 to August 2023. Utilizing our hospital's database, we systematically extracted these patients' information. We monitored the survival time and constructed Kaplan-Meier (K-M) survival curve. Through Cox proportional hazards regression analyses, independent risk factors were identified. Based on these factors, a survival prediction model was developed and its reliability was evaluated by the receiver operating characteristic (ROC) curve. In addition, patients who refused surgery were excluded, the eligible patients were divided into a long waiting group (> 48 h) and a short waiting group (≤ 48 h). According to a similar process, independent risk factors were identified. Another nomogram chart and ROC curve were conducted. RESULTS: Data from 174 patients were used, presenting a median survival time of 40 months. Both univariate and multivariate analyses identified age (HR = 1.71, 95% CI: 1.26-2.32), surgical intervention (HR = 0.34, 95% CI: 0.21-0.55), number of comorbidities (HR = 1.44, 95% CI: 1.09-1.92) and lymphocyte levels (HR = 0.75, 95% CI: 0.61-0.92) as independent influence factors. Based on these factors, a nomogram chart was constructed. The areas under the ROC curve for predicting 1-year, 2-year, and 3-year survival rates were 0.748, 0.794 and 0.806 respectively. Additionally, through regression analysis of surgical patients, some factors (age, number of comorbidities and lymphocyte levels) were supported as independent influence factors. CONCLUSION: Advanced age, non-surgical management, multiple comorbidities and lower lymphocyte levels showed a higher risk of all-cause mortality among the patients with HRFs, and these factors were associated with a poor prognosis in this patient population. This study may be useful for improving these patients' prognosis.
INTRODUCTION: The purpose of this study is to evaluate the increase in bone mineral density (BMD) and achievement of treatment goals based on the ASBMR/BHOF position statement over 3 years of sequential therapy with 2 ye...INTRODUCTION: The purpose of this study is to evaluate the increase in bone mineral density (BMD) and achievement of treatment goals based on the ASBMR/BHOF position statement over 3 years of sequential therapy with 2 years of twice-weekly teriparatide (2/W TPTD) followed by 1 year of bisphosphonate (BP) therapy. MATERIALS AND METHODS: This was a multicenter, retrospective study. Thirty-eight postmenopausal patients with primary osteoporosis at very high risk of fracture according to the Diagnostic Criteria for Primary Osteoporosis in Japan were enrolled. Changes in BMD at the lumbar spine (LS) and total hip (TH) were evaluated. Patients were divided into the naïve group (no history of osteoporosis treatment) and the pre-BP group (prior BP treatment). The treatment goals were assessed using the BMD T-score as follows; Baseline T-score ≤ - 2.5: Greater than - 2.5 at 3 years and baseline T-score > - 2.5: Increase at least 0.5 for LS and 0.2 for TH. RESULTS: The naïve group showed a significant increase in LS-BMD and TH-BMD of 14.6% and 4.8%, respectively, and the pre-BP group only showed a significant increase in LS-BMD of 8.4% over 3 years. In the naïve group, 60.7% (17/28) achieved the treatment goal for LS-BMD, and 39.3% (11/28) achieved for TH-BMD. In the pre-BP group, 50.0% (4/8) achieved the treatment goal for LS-BMD, but no patient achieved the goal for TH-BMD. CONCLUSION: After 3 years of sequential therapy from 2/W TPTD to BP, 50% or more of the patients achieved the treatment goal in the LS-BMD but not in the TH-BMD.
Iwata E, Ohori H, Susukida Y
… +8 more, Yatagai N, Kashin M, Matsui T, Takata N, Kobayashi M, Miyai D, Tachibana A, Akashi M
J Bone Miner Metab
· 2025 Sep · PMID 40601030
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BACKGROUND: There are no established guidelines for antibiotic administration to prevent the development of medication related-osteonecrosis of the jaw (MRONJ) after tooth extraction in patients receiving antiresorptive...BACKGROUND: There are no established guidelines for antibiotic administration to prevent the development of medication related-osteonecrosis of the jaw (MRONJ) after tooth extraction in patients receiving antiresorptive agents (ARAs). Since 2022, the duration of antibiotic administration during extractions in such patients has been intentionally shortened to prevent antimicrobial resistance at our hospitals. METHODS: This retrospective study involved 160 patients on low-dose bisphosphonates (BPs) requiring tooth extractions between 2019 and 2024 at four Japanese institutions. In 2019-2021, patients received amoxicillin (AMPC) 500 mg 1 h before and 750 mg per day for 2 days post-extraction. In 2022-2024, a single 500 mg dose of AMPC was administered 1 h pre-extraction. Patients were managed with tension-free wound suturing and regular follow-up. The rates of MRONJ development were compared between the two periods. RESULTS: MRONJ developed in 3 out of 170 teeth (1.76%) in 2019-2021, and in 2 out of 147 teeth (1.36%) in 2022-2024, with no significant difference (P = 1.000). All MRONJ cases were low-stage (Stage 1) and healed completely within 12-16 weeks. Four out of five MRONJ cases (80%) exhibited radiopaque changes around the root. When all teeth in both groups were surveyed, MRONJ development was significantly higher in teeth with such changes compared to those without (4/58 vs. 1/259; P = 0.004). CONCLUSION: A single preoperative dose of AMPC may be sufficient for tooth extractions in patients on low-dose BPs. However, teeth with radiopaque changes around the root require careful monitoring postextraction.
Tsutsui T, Fujiwara T, Matsumoto Y
… +24 more, Kimura A, Kanahori M, Arisumi S, Oyamada A, Ohishi M, Ikuta K, Tsuchiya K, Tayama N, Tomari S, Miyahara H, Mae T, Hara T, Saito T, Arizono T, Kawano T, Mawatari T, Fujiwara M, Takasaki M, Shin K, Ninomiya K, Nakaie K, Antoku Y, Iwamoto Y, Nakashima Y
INTRODUCTION: Fragility hip fracture (FHF) has been frequently seen in trauma of older people, resulted in decreased mobility and a loss of independence. MATERIALS AND METHODS: This study retrospectively assessed the lon...INTRODUCTION: Fragility hip fracture (FHF) has been frequently seen in trauma of older people, resulted in decreased mobility and a loss of independence. MATERIALS AND METHODS: This study retrospectively assessed the long-term health-related quality of life (HRQOL) and living arrangement in older patients following FHF, and evaluated the factors associating with long-term EuroQol 5D (EQ5D) for 5 years or more. This study included 203 Japanese patients (male 26, female 177) with FHF over the age of 60 years. We examined the long-term EQ5D and life style at final follow-up, and identified the factors affecting with EQ5D. RESULTS: The mean age at baseline of 79 years, the mean observation duration was 6 years, and the average value of EQ5D at final follow-up was 0.65. Multivariate analysis presented that EQ5D at final follow-up was significantly predicted by serum albumin, trochanteric fracture, comorbidity stroke, higher BI at post-admission, less length of stay hospital, and living at home at final follow-up. The people living at home at final follow-up (148/203 [72.9%]) was less than the people at baseline (190/203 [93.6%]). In multivariate analysis, the people living at home at final follow-up were younger age at baseline, and higher BI at post-admission. DISCUSSION: In conclusion the long-term EQ5D after FHF was decreased in patients with lower serum albumin at baseline, with trochanteric fracture, with stroke comorbidity, and with lower BI at post-admission. The people living at home after FHF were young age at baseline and high BI at post-admission.
Mori Y, Tarasawa K, Tanaka H
… +4 more, Mori N, Fushimi K, Aizawa T, Fujimori K
J Bone Miner Metab
· 2025 Sep · PMID 40593307
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INTRODUCTION: Type 2 diabetes is associated with an increased risk of fragility fractures, even in individuals with normal or high bone mineral density. However, the impact of type 2 diabetes on postoperative outcomes af...INTRODUCTION: Type 2 diabetes is associated with an increased risk of fragility fractures, even in individuals with normal or high bone mineral density. However, the impact of type 2 diabetes on postoperative outcomes after hip fracture surgery in elderly Japanese patients remains unclear. This study evaluated the association between type 2 diabetes and postoperative complications, including in-hospital mortality, using a nationwide database in Japan. MATERIALS AND METHODS: A retrospective cohort study was conducted using the Diagnosis Procedure Combination (DPC) database from April 2016 to March 2022. Patients aged ≥ 65 years who underwent hip fracture surgery were included. Propensity score matching (1:1) was performed to adjust for confounders. Logistic regression analyses were used to assess associations between type 2 diabetes and outcomes. RESULTS: Of the 474,293 eligible patients included in this study, 18.5% were identified as having comorbid type 2 diabetes. Following 1:1 propensity score matching, the final analytic cohorts each comprised 83,283 patients. Although statistically significant, the presence of type 2 diabetes was associated with only modest increases in the risks of postoperative myocardial infarction (risk difference [RD]: 0.0007), cognitive dysfunction (RD: 0.0029), and in-hospital mortality (RD: 0.0045), with all comparisons yielding p-values of less than 0.0001. Additionally, the length of hospital stay was longer among patients with type 2 diabetes. CONCLUSIONS: Although the absolute risk differences were small, type 2 diabetes remains an independent risk factor for adverse postoperative outcomes following hip fracture surgery in elderly Japanese patients. Tailored perioperative strategies may help optimize outcomes in this vulnerable population.
Hanaka M, Iba K, Takada J
… +11 more, Sonoda T, Kozakai Y, Oda T, Ishikawa I, Tateda K, Fujita Y, Jimbo S, Matsumura T, Emori M, Teramoto A, Katahira G
INTRODUCTION: Fracture Liaison Service (FLS) programs are beneficial for reducing the frequency of subsequent fractures and mortality in post-hip fracture patients. The aim of this study was to investigate recent changes...INTRODUCTION: Fracture Liaison Service (FLS) programs are beneficial for reducing the frequency of subsequent fractures and mortality in post-hip fracture patients. The aim of this study was to investigate recent changes in the rate of pharmaceutical treatment for osteoporosis in post-hip fracture surgery patients in the absence of FLS programs compared to the previous 10 and 20 years, and whether introduction of a new reimbursement scheme in hip fracture care, launched in 2022 by the Japanese government, improved the pharmaceutical treatment rate after surgical intervention. MATERIALS AND METHODS: Study 1 included 1490 post-hip fracture patients in seven hospitals without an FLS program. Study 2 included 396 osteoporosis patients who were covered by the new reimbursement scheme at five of the seven hospitals. Treatment-related variables and the number of patients who received the different pharmaceutical treatments at 0, 3, 6 and 12 months after discharge from the hospital were examined. RESULTS: Two hundred and thirty-two of 1474 patients received anti-osteoporotic medication at hospital discharge, which was not a significant improvement in the rate of pharmaceutical treatment in comparison with that in our previous studies over 20 years. On the other hand, introduction of the new reimbursement scheme at hospitals significantly improved the rate of pharmaceutical treatment, with 263 of the 391 patients receiving anti-osteoporotic medication at discharge, as well as a significant improvement. CONCLUSION: We demonstrated a significant improvement in the pharmaceutical treatment rate for osteoporosis in post-hip fracture surgery patients after introduction of the new reimbursement scheme launched by the Japanese government.