Osteoporotic Bone Regeneration via Plenished Biomimetic PLGA Scaffold with Sequential Release System.

Achieving satisfactory bone tissue regeneration in osteoporotic patients with ordinary biomaterials is challenging because of the decreased bone mineral density and aberrant bone microenvironment. In addressing this issue, a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold with magnesium hydroxide (M) and extracellular matrix (E) is introduced, enabling the consecutive release of bioactive agents. 4HR and SP induced the phosphorylation of p38 MAPK and ERK in human umbilical vein endothelial cells (HUVECs), thereby upregulating VEGF expression level. The migration and tube-forming ability of endothelial cells can be promoted by the scaffold, which accelerates the formation and maturation of the bone. Moreover, 4HR played a crucial role in the inhibition of osteoclastogenesis by interrupting the IκB/NF-κB signaling pathway and exhibiting SP, thereby enhancing the migration and angiogenesis of HUVECs. Based on such a synergistic effect, osteoporosis can be suppressed, and bone regeneration can be achieved by inhibiting the RANKL pathway in vitro and in vivo, which is a commonly known mechanism of bone physiology. Therefore, the study presents a promising approach for developing a multifunctional regenerative material for sophisticated osteoporotic bone regeneration.

Chemokine CXCL9, a marker of inflammaging, is associated with changes of muscle strength and mortality in older men.

Our study examined associations of the CXC motif chemokine ligand 9 (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with musculoskeletal function in elderly men. We found in certain outcomes both cross-sectional and longitudinal significant associations of CXCL9 with poorer musculoskeletal function and increased mortality in older men. This requires further investigation. PURPOSE: We aim to determine the relationship of (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with both cross-sectional and longitudinal musculoskeletal outcomes and mortality in older men. METHODS: A random sample from the Osteoporotic Fractures in Men (MrOS) Study cohort (N = 300) was chosen for study subjects that had attended the third and fourth clinic visits, and data was available for major musculoskeletal outcomes (6 m walking speed, chair stands), hip bone mineral density (BMD), major osteoporotic fracture, mortality, and serum inflammatory markers. Serum levels of CXCL9 were measured by ELISA, and the associations with musculoskeletal outcomes were assessed by linear regression and fractures and mortality with Cox proportional hazards models. RESULTS: The mean CXCL9 level of study participants (79.1 ± 5.3 years) was 196.9 ± 135.2 pg/ml. There were significant differences for 6 m walking speed, chair stands, physical activity scores, and history of falls in the past year across the quartiles of CXCL9. However, higher CXCL9 was only significantly associated with changes in chair stands (ß = - 1.098, p < 0.001) even after adjustment for multiple covariates. No significant associations were observed between CXCL9 and major osteoporotic fracture or hip BMD changes. The risk of mortality increased with increasing CXCL9 (hazard ratio quartile (Q)4 vs Q1 1.98, 95% confidence interval 1.25-3.14; p for trend < 0.001). CONCLUSIONS: Greater serum levels of CXCL9 were significantly associated with a decline in chair stands and increased mortality. Additional studies with a larger sample size are needed to confirm our findings.

Osteoporotic vertebral fractures localized in the lumbar area significantly impact sagittal alignment.

Lumbar fractures and/or multiple fractures at the lumbar or thoracolumbar regions are risk factors for sagittal malalignment in patients older than 70 years old. Although patients with OVF show a huge capacity to compensate after the fractures, lumbar and TL lumbar fractures require closer monitoring. PURPOSE: To assess the impact of osteoporotic vertebral fractures on the sagittal alignment of the elderly and identify risk factors for sagittal malalignment. METHODS: We performed a retrospective study on a cohort of 249 patients older than 70 years old and diagnosed with osteoporosis who suffered chronic vertebral fractures. Demographic and radiological data were collected. Full-spine lateral X-rays were obtained to analyze the sagittal plane. Patients were classified according to the number and location of the fractures. Pearson's correlation coefficient was used to assess the relationships between the type of fractures and sagittal alignment. RESULTS: A total of 673 chronic fractures were detected in 249 patients with a mean number of vertebral fractures per patient of 2.7 ± 1.9. Patients were divided into 9 subgroups according to the location and the number of fractures. Surprisingly, any of the aggregated parameters used to assess sagittal alignment exceeded the threshold defined for malalignment. In the second part of the analysis, 41 patients with sagittal malalignment were identified. In this subpopulation, an overrepresentation of patients with lumbar fractures (34% vs. 11%) and an under-representation of thoracic fractures (9% vs. 34%) were reported. We also observed that patients with 3 or more lumbar or thoracolumbar fractures had an increased risk of sagittal malalignment. CONCLUSIONS: Lumbar fractures and/or multiple fractures at the lumbar or thoracolumbar regions are risk factors for sagittal malalignment in patients older than 70 years old. Although patients show a remarkable capacity to compensate, fractures at the lumbar and thoracolumbar regions need closer monitoring.

The association between myasthenia gravis and risk of fracture: a systematic review and meta-analysis.

Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for osteoporosis or fracture. However, clinical evidence of this issue is lacking. In this review, we systematically searched databases, including Cochrane Library, PubMed, Embase, and Airiti library from inception to the end of November 2023 for cohort studies that compared participants with MG and participants without MG for incidence of osteoporosis or fracture. We used the Newcastle-Ottawa Scale for quality assessment. In total, we included 3 studies with 34,865 participants. The pooled meta-analysis using the random effect model demonstrated no significant difference in risk of fracture in the MG group (odds ratio = 1.52; 95% confidence interval = 0.74 to 3.12; I2 = 93%; between-study variance [τ2] = 0.32) compared with that for the non-MG group. Due to limited studies, we could not perform a quantitative analysis for risk of osteoporosis. In conclusion, we found no robust evidence to support the proposition that patients with MG are at higher risk for fracture than general comparators. The explanations and underlying mechanisms of this finding remain unclear, we therefore conclude that additional studies are warranted.

Sex differences in hemoglobin levels and five-year refracture risk in patients with osteoporotic fractures: a retrospective cohort analysis.

We conducted a retrospective cohort analysis to examine the association between hemoglobin (Hb) levels and refracture risk in elderly patients with osteoporotic fractures (OPFs). Our findings suggest a nonlinear relationship exists in females, and females with Hb levels below 10.7 g/dL may be at a higher risk of refracture. INTRODUCTION: Hematopoiesis and bone health have a reciprocal influence on each other. Nevertheless, there is a scarcity of in-depth research on the association between Hb levels and the occurrence of fractures. The present research aimed to investigate the correlation between Hb levels and the rate of refracture within 5 years among individuals with OPFs. METHODS: A retrospective cohort analysis was undertaken between 2017 and 2022. The study included 1906 individuals who were inhabitants of Kunshan and were over 60 years old. These individuals had experienced an OPF between January 1, 2017, and July 27, 2022, resulting in their hospitalization. Cox proportional hazard regression models were used to evaluate the risk of refracture within 5 years based on the Hb levels acquired during the admission examination, with consideration for sex differences. A nonlinear relationship was identified using smoothed curve fitting and threshold analysis. Kaplan-Meier curves were used to compare refracture rates between patients with low and high Hb levels. RESULTS: Elderly female patients with OPFs and lower Hb levels exhibited a significantly higher risk of a 5-year refracture. Conversely, no significant associations were observed between the two variables in male patients. A nonlinear correlation was found between Hb levels and the probability of refracture in females, with a turning point identified at 10.7 g/dL of Hb levels. A strong negative association was observed with the five-year refracture rate when Hb levels fell below 10.7 g/dL (hazard ratio (HR) = 0.63; 95% confidence interval (CI) 0.48 to 0.83; P-value = 0.0008). This finding suggests that for every 1 g/dL increase in Hb below 10.7 g/dL, the risk of refracture reduced by 37%. However, no statistically significant association was observed when Hb levels were above 10.7 g/dL. CONCLUSIONS: The findings demonstrated a significant negative correlation between Hb levels and the likelihood of refracture in elderly female patients with OPFs and suggested that elderly females with recent OPFs and Hb levels below 10.7 g/dL may be at a higher risk of refracture. Additionally, the Hb levels can serve as an indicator of bone fragility in elderly female patients with OPFs. These findings highlight the importance of monitoring Hb levels as a part of comprehensive management strategies to both assess skeletal health and prevent refractures in this population.

Association of bone fracture with 30-year body mass index (BMI) trajectories: findings from the Framingham Heart Study : Bone fracture and 30-year BMI trajectories.

A knowledge gap exists in associating later life's osteoporotic fracture and middle adulthood's BMI trajectories. We observed an association showing those transitioning from overweight to normal weight face a higher fracture risk in late adulthood, emphasizing the potential benefits of maintaining a stable BMI to reduce late-life fractures. PURPOSE: Numerous studies on the relationship between obesity and fractures have relied on body mass index (BMI) at a single time point, yielding inconclusive results. This study investigated the association of BMI trajectories over middle adulthood with fracture risk in late adulthood. METHODS: This prospective cohort study analyzed 1772 qualified participants from the Framingham Original Cohort Study, with 292 (16.5%) incident fractures during an average of 17.1-year follow-up. We constructed BMI trajectories of age 35-64 years based on latent class mixed modeling and explored their association with the risk of fracture after 65 years using the Cox regression. RESULTS: The result showed that compared to the BMI trajectory Group 4 (normal to slightly overweight; see "Methods" for detailed description), Group 1 (overweight declined to normal weight) had a higher all-fracture risk after age 65 (hazard ratio [HR], 2.22, 95% CI, 1.13-4.39). The secondary analysis focusing on lower extremity fractures (pelvis, hip, leg, and foot) showed a similar association pattern. CONCLUSIONS: This study suggested that people whose BMI slightly increased from normal weight to low-level overweight during 30 years of middle adulthood confer a significantly lower risk of fracture in later life than those whose BMI declined from overweight to normal weight. This result implies the potentially beneficial effects of avoiding weight loss to normal weight during middle adulthood for overweight persons, with reduced fracture risk in late life.

Understanding the long-term impact of incident osteoporotic fractures on healthcare utilization and costs in Korean postmenopausal women.

This study provides long-term evidence that healthcare resource utilization and costs of care in women who experienced incident osteoporotic fractures remained higher than those in women without fractures over a span of 5 years. These findings emphasize the importance of early diagnostics and treatment for osteoporosis. PURPOSE: To evaluate healthcare resource utilization (HCRU) and costs of care over 5 years after the incident osteoporotic fractures (OF) in postmenopausal women. METHODS: We used data from the National Health Insurance Service databases 2011-2018. Women aged ≥ 50 years with incident OF (OF group) were matched to women without OF (non-OF group). HCRU (inpatient, outpatient, and emergency room [ER] visits) and costs of care (inpatient, outpatient, and ER visits) during the 5-year follow-up period were derived after propensity score matching (PSM). Additionally, we identified women with subsequent fractures within the first 2 years after the incident OF. RESULTS: After PSM, 47,238 OF and 134,813 non-OF women were identified. HCRU rates and costs of care were highest in the first year after OF and decreased substantially, but remained higher in the OF group during the entire follow-up period. The increase in cumulative HCRU rates over 5 years was highest in inpatient admissions with ER visits (138% higher in OF vs non-OF). The cumulative total costs over 5 years were 73% higher in the OF group than in the non-OF group, which was mostly driven by inpatient costs. Trends were similar for women with subsequent fractures, but they generally showed higher HCRU and costs than those in the total OF group. CONCLUSION: OF imposes a substantial and sustained economic burden on women, resulting in an approximately twofold increase in the cumulative cost over 5 years compared to women without fracture, which highlights the need for early diagnostics and treatment of osteoporosis.

Non-osteoporotic fractures are associated with increased risk of subsequent major osteoporotic fractures.

We studied the association between non-osteoporotic fractures and future major osteoporotic fractures, using UK health records. Non-osteoporotic fractures were found to increase the risk of major osteoporotic fractures, although to a lesser extent than osteoporotic fractures. This highlights the importance of considering all previous fractures in assessing future fracture risk. PURPOSE: Previous studies demonstrated that osteoporotic fractures-minor and major-increase the risk for future major osteoporotic fractures; we test whether non-osteoporotic fractures are also associated with such increased risk. METHODS: The study is a retrospective cohort study using UK primary care electronic health records. Exposure groups were defined according to fracture location prior to the year 2011 (index date): major, minor, and non-osteoporotic. The outcome of incident major osteoporotic fractures following the index date was compared between the exposure groups and the general population. RESULTS: The general study population included 1,951,388 patients. The exposure groups included 39,931 patients with a prior major osteoporotic fracture, 19,397 with a prior minor osteoporotic fracture, and 50,115 patients with a prior non-osteoporotic fracture. The standardized Incidence Rate Ratio for future major osteoporotic fractures was 2.73 (95% confidence interval: 2.64-2.82), 2.43 (2.32-2.54), and 1.83 (1.74-1.92), respectively. CONCLUSION: Non-osteoporotic fractures are significantly associated with increased risk for future major osteoporotic fractures relative to the general population, yet to a lesser extent compared to major and minor osteoporotic fractures.

Fracture liaison service-a multidisciplinary approach to osteoporosis management.

A fracture liaison service is a systems-level multidisciplinary approach designed to reduce subsequent fracture risk in patients who recently sustained fragility fractures. It is estimated that one in three women and one in five men over the age of 50 years old have osteoporosis. Nonetheless, only 9 to 20% of patients who sustain an initial fragility fracture eventually receive any osteoporosis treatment. With the aim of preventing subsequent fractures, a fracture liaison service (FLS) works through identifying patients presenting with fragility fractures to the hospital and providing them with easier access to osteoporosis care through referrals for bone health and fracture risk assessment and recommendation or initiation of osteoporosis treatment. Currently, there are four major types of FLS models ranging from services that only identify at-risk patients and inform and educate the patient but take no further part in communicating their findings to other stakeholders in patients' care, to services that identify, investigate, and initiate treatment at the other end of the spectrum. In this article, we review the benefits, challenges, and outcomes of FLS in the American healthcare system with further exploration of the roles each member of the multidisciplinary team can play in improving patients' bone health.

Total knee arthroplasty and periprosthetic distal femoral fracture: looking beyond the osteoporosis to previous osteoporotic fracture.

Osteoporosis increases the risk of periprosthetic distal femoral fractures after TKA, especially in patients with a history of osteoporotic fractures. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized by the patients following primary TKA. PURPOSE: Osteoporosis is a risk factor for fractures, including those of the hip, vertebrae, and distal radius; however, the association between osteoporosis and periprosthetic fractures after total knee arthroplasty (TKA) has not been much investigated. Therefore, we aimed to investigate the association of the presence of systemic osteoporosis with periprosthetic fractures after TKA. METHODS: This study included 34 patients with periprosthetic fractures following primary TKA and 106 controls matched for age and sex. Bone mineral density was evaluated at the femoral neck, total hip, and lumbar spine using dual X-ray absorptiometry. Medical records were reviewed for age; sex; body mass index; smoking; rheumatoid arthritis, endocrine diseases, and cardiovascular diseases; history of glucocorticoid use; medication for osteoporosis; and history of previous osteoporotic fracture. In addition, anterior femoral notching after TKA was evaluated. Univariable and multivariable logistic regression analysis were used to determine factors associated with periprosthetic fracture. RESULTS: The prevalence of osteoporosis in the fracture group was higher than that in the control group (61.8% vs. 40.6%, p=0.045). The rate of medication for osteoporosis was significantly low in the fracture group (47.6 % vs 76.7%, p=0.026). History of previous osteoporotic fracture (odds ratio [OR], 9.1; p=0.015) and osteoporosis (OR, 3.6; p=0.013) were significant risk factors for periprosthetic fractures after TKA. Medication for osteoporosis could decrease the risk of periprosthetic fracture (OR 0.3; p=0.020). CONCLUSION: Osteoporosis is a major risk factor for periprosthetic distal femoral fractures after TKA. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized to the patients following primary TKA, especially in patients with a history of osteoporotic fracture. LEVEL OF EVIDENCE: Prognostic study, level III.

Should major trauma fractures be part of a fracture liaison service's remit: a cost-benefit estimate.

The refracture rate after major trauma is approximately half (57%) the refracture rate after a minimal trauma injury. Extending Fracture Liaison Service activity to include major trauma patients creates significant additional direct cost, but remains essentially cost neutral if notional savings through refracture risk reduction are taken into account. PURPOSE: To compare the 3-year refracture rate following minimal trauma (MT) and non-minimal trauma (non-MT) injuries and evaluate the cost of extending fracture liaison service (FLS) operations to non-MT presentations. METHODS: Patients aged 50, or above presenting to the John Hunter Hospital with a fracture in calendar year 2018 were identified through the Integrated Patient Management System (IPMS) of the Hunter New England Health Service's (HNEHS), and re-presentation to any HNEHS facility over the following 3 years monitored. The refracture rate of MT and non-MT presentations was compared and analysed using Cox proportional hazards regression models. The cost of including non-MT patients was estimated through the use of a previously conducted micro-costing analysis. The operational fidelity of the FLS to the previous estimate was confirmed by comparing the 3-year refracture rate of MT presentations in the two studies. RESULTS: The 3-year refracture rate following a MT injury was 8% and after non-MT injury 4.5%. Extension of FLS activities to include non-MT patients in 2022 would have cost an additional $198,326 AUD with a notional loss/saving of $ - 26,625/ + 26,913 AUD through refracture risk reduction. No clinically available characteristic at presentation predictive of increased refracture risk was identified. CONCLUSION: The 3-year refracture after a non-MT injury is about half (57%) that of the refracture rate after a MT injury. Extending FLS activity to non-MT patients incurs a significant additional direct cost but remains cost neutral if notional savings gained through reduction in refracture risk are taken into account.

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.

Changes in spinal sagittal balance after a new osteoporotic vertebral compression fracture.

We conduct a longitudinal study to examine how new VCF alter spinal sagittal balance. New VCF increased SVA by an average of 2.8 cm. Sagittal balance deteriorates as a VCF develops in the lower lumbar spine. A new fracture below L1 increased the relative risk of a deterioration of sagittal balance 2.9-fold compared to one above Th12. PURPOSE: Studies on the relationship between osteoporotic vertebral fractures and spinal sagittal balance have all been limited to cross-sectional studies. The aim of this study is to conduct a longitudinal study to examine how new vertebral compression fracture (VCF) alter spinal sagittal balance. METHODS: Subjects were patients undergoing periodic examinations after treatment of a vertebral fracture or lumbar spinal canal stenosis. Forty patients who developed a new VCF were included in this study. Full-spine standing radiographs were compared before and after the fracture to examine changes in spinopelvic parameters and factors determining the changes in sagittal balance. RESULTS: The mean age of the patients was 79.0 years. The mean interval between pre- and post-fracture radiographs was 22.7 months, and the mean time between development of a fracture and post-fracture radiographs was 4.6 months. After a fracture, sagittal vertical axis (SVA) increased an average of 2.78 cm and spino-sacral angle (SSA) decreased an average of 5.3°. Both ⊿SVA and ⊿SSA were not related to pre-fracture parameters. The wedge angle of the fractured vertebra was not related to changes in sagittal balance. ⊿SVA increased markedly in patients with a fracture of the lower lumbar vertebrae. receiver operating characteristic analysis revealed that the relative risk of a deterioration of sagittal balance was 2.9 times higher for a new fracture below L1 than for a fracture above Th12. CONCLUSION: New VCF increased SVA by an average of 2.8 cm. Sagittal balance deteriorates as a new fracture develops in the lower lumbar spine. Early intervention in osteoporosis is vital for the elderly.

Osteosarcopenia: Prevalence and 10-Year Fracture and Mortality Risk - A Longitudinal, Population-Based Study of 75-Year-Old Women.

Osteosarcopenia is the coexistence of low bone mass and sarcopenia. In older women, its prevalence is not well described, and it is unknown if sarcopenia is additive to low bone mass for fracture and mortality risk. The study investigated prevalence of osteosarcopenia and if osteosarcopenia is associated with higher fracture and mortality risk than low bone mass alone in older community-dwelling women. The longitudinal, population-based OPRA Cohort (n = 1044), all aged 75 at inclusion, followed for 10 years. Using WHO and EWGSOP2 definitions for low bone mass (T-score < -1.0 femoral neck) and sarcopenia (knee strength; appendicular lean muscle mass) women were categorized (1) Normal, (2) Low bone mass (LBM), and 3) Osteosarcopenia (probable; confirmed). Risk of hip, major osteoporotic fracture, and mortality were estimated. Osteosarcopeniaconfirmed prevalence increased from age 75 to 80 and 85 from 3.0% (29/970) to 4.9% (32/656) to 9.2% (33/358) but prevalence is potentially 2-4 times higher (11.8%, 13.4%, 20.3%) based on osteosarcopeniaprobable. Having osteosarcopeniaprobable significantly increased 10-year risk of hip fracture (HRadj 2.67 [1.34-5.32]), major osteoporotic fracture (HRadj 2.04 [1.27-3.27]), and mortality (HRadj 1.91 [1.21-3.04]). In contrast, LBM increased osteoporotic fracture risk (HRadj 2.08 [1.46-2.97], but not hip fracture (HRadj 1.62 [0.92-2.85]) or mortality (HRadj 0.94 [0.64-1.38]). Median time-to-hip fracture was 7.6 years (normal), 6.0 years (LBM), and 5.7 years (osteosarcopeniaprobable). Prevalence of confirmed osteosarcopenia is almost 10% at age 85. Probable osteosarcopenia significantly increased risk of hip and major osteoporotic fractures and mortality more so than low bone mass alone.

Comparison of the Clinical Outcomes of Vesselplasty vs. Percutaneous Vertebroplasty for the Treatment of Neurologically Intact Osteoporotic Kümmell's Disease: A Retrospective Study.

Kummell's disease (KD) is a rare clinical complication of osteoporotic vertebral compression fractures (OVCFs). Minimally invasive surgery is an important way to treat KD. In this paper, we used Percutaneous Vertebroplasty (PVP) and Vesselplasty (VP) to treat KD. 125 patients with KD were admitted to our hospital. Among them, 89 patients received PVP and 36 received VP. All patients underwent operations successfully. VAS scores and ODI of both groups at each postoperative time point were lower than preoperatively. Postoperative Cobb angle of both groups postoperatively was lower than preoperatively (p < 0.05). The anterior height and ratio of vertebra compression of both groups postoperatively was lower than preoperatively (p < 0.05). Cement leakage occurred in 16 vertebrae (16/89) in PVP group and one (1/36) in VP group. Two patients suffered from transient paraplegia in PVP group immediately after operation. Adjacent vertebral fractures occurred in one patient in PVP group and one in VP group. Re-fracture of affected vertebra occurred in one patient in PVP group. Besides, four patients suffered from bone cement loosening in PVP group while one in VP group. Both PVP and VP play an important effect in pain relief and functional recovery for the treatment of KD. And VP is more effective than PVP in preventing cement leakage.

Risk of adjacent level fracture after percutaneous vertebroplasty and kyphoplasty vs natural history for the management of osteoporotic vertebral compression fractures: a network meta-analysis of randomized controlled trials.

OBJECTIVES: Percutaneous vertebroplasty and kyphoplasty are common interventions for osteoporotic vertebral compression fractures. However, there is concern about an increased risk of adjacent-level fractures after treatment. This study aimed to compare the risk of adjacent-level fractures after vertebroplasty and kyphoplasty with the natural history after osteoporotic vertebral compression fractures. MATERIALS AND METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to the natural history after osteoporotic vertebral compression fractures. Frequentist network meta-analysis was conducted using the "netmeta" package, and heterogeneity was assessed using Q statistics. The pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using random effects. RESULTS: Twenty-three RCTs with a total of 2838 patients were included in the analysis. The network meta-analysis showed comparable risks of adjacent-level fractures between vertebroplasty, kyphoplasty, and natural history after osteoporotic vertebral compression fractures with a mean follow-up of 21.2 (range: 3-49.4 months). The pooled RR for adjacent-level fractures after kyphoplasty compared to natural history was 1.35 (95% CI, 0.78-2.34, p = 0.23) and for vertebroplasty compared to natural history was 1.16 (95% CI, 0.62-2.14) p = 0.51. The risk of bias assessment showed a low to moderate risk of bias among included RCTs. CONCLUSION: There was no difference in the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to natural history after osteoporotic vertebral compression fractures. The inclusion of a large patient number and network meta-analysis of RCTs serve evidence-based clinical practice. CLINICAL RELEVANCE STATEMENT: The risk of adjacent-level fracture following percutaneous vertebroplasty or kyphoplasty is similar to that observed in the natural history after osteoporotic vertebral compression fractures. KEY POINTS: RCTs have examined the risk of adjacent-level fracture after intervention for osteoporotic vertebral compression fractures. There was no difference between vertebroplasty and kyphoplasty patients compared to the natural disease history for adjacent compression fractures. This is strong evidence that interventional treatments for these fractures do not increase the risk of adjacent fractures.

Drug utilization pattern of romosozumab and other osteoporosis treatments in Japan, 2019-2021.

INTRODUCTION: Describe real-world treatment of osteoporosis and romosozumab treatment patterns in Japan. MATERIALS AND METHODS: Data for patients initiating romosozumab or other antiosteoporotic medications between March 01, 2018, and May 31, 2022, were extracted from the Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. Patients were categorized into four cohorts: those who newly initiated romosozumab within the first (MDV: n = 4782; JMDC: n = 2578) or second (MDV: n = 3888; JMDC: n = 2446) year after launch and those who initiated teriparatide (TPTD; MDV: n = 14,576; JMDC: n = 8259) or non-TPTD antiosteoporotic medications within the first year of romosozumab launch (MDV: n = 352,142; JMDC: n = 185,785). RESULTS: Mean age, sex, baseline cardiovascular history, comorbidities, and concomitant medications were similar across cohorts. In the MDV database, fracture history was higher in the romosozumab year-1 (59.3%), year-2 (64.1%), and TPTD (65.5%) cohorts versus the non-TPTD cohort (24.4%). Similar rates were identified in the JMDC database: romosozumab year-1 (64.7%), year-2 (66.6%), TPTD (67.5%), and non-TPTD (27.8%). Vertebral fractures were most common in all cohorts. 12-month romosozumab discontinuation varied between the year-1 and year-2 cohorts in MDV (62.4% and 58.8%) and JMDC (57.1% and 52.7%), whereas mean number of injections remained consistent (MDV: 9.7 and 9.8; JMDC: 7.3 and 7.8). Romosozumab persistence was lower in year-1 versus year-2 (MDV: 37.6% and 42.9%; JMDC: 41.2% and 47.3%). CONCLUSION: Patients initiating romosozumab and TPTD had a high fracture history. Given the dual effects of promoting bone formation and suppressing resorption, improving romosozumab adherence and persistence over time may be important for antiosteoporotic therapy.

The predictive value of albumin to alkaline phosphatase ratio for vertebral refractures in postmenopausal women.

INTRODUCTION: To investigate the clinical value of serum albumin to alkaline phosphatase ratio (AAPR) in predicting the risk of osteoporotic vertebral refractures group (OVRFs) after percutaneous vertebral augmentation (PVA) in postmenopausal women. MATERIALS AND METHODS: This is a retrospective case-control study including a series of postmenopausal women patients with osteoporotic vertebral fracture (OVF) and underwent PVA. Patients were divided into OVRFs and non-OVRFs. COX model was used to evaluate the correlation between preoperative AAPR and OVRFs after PVA. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were used to analyze the predictive value of AAPR for the incidence of OVRFs. RESULTS: A total of 305 patients were included in the final study, and the incidence of postoperative OVRFs was 28.9%. Multivariate COX analysis showed that advanced age (HRs = 1.062, p = 0.002), low BMI (HRs = 0.923, p = 0.036), low AAPR (HRs = 0.019, p = 0.001), previous fall history (HRs = 3.503, p = 0.001), denosumab treatment (HRs = 0.409, p = 0.007), low L3 BMD (HRs = 0.977, p = 0.001) and low L3 paravertebral muscle density (PMD)value (HRs = 0.929, p = 0.001)) were closely related to the incidence of OVRFs. The area under the curve (AUC) of AAPR for predicting OVRFs was 0.740 (p < 0.001), and the optimal diagnostic cut-off value was 0.49. Kaplan-Meier curve analysis showed that low AAPR group (< 0.49) was significantly associated with lower OVRFs-free survival (p = 0.001; log-rank test). CONCLUSION: AAPR is an independent risk factor for OVRFs after PVA in postmenopausal women, and it can be used as an effective index to predict OVRFs.

Melatonin rescues the mitochondrial function of bone marrow-derived mesenchymal stem cells and improves the repair of osteoporotic bone defect in ovariectomized rats.

Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow-derived mesenchymal stem cells (BMMSCs) are the primary origin of bone-forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well-known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs. In vitro administration of melatonin at varying concentrations (0.01, 1, and 100 µM) demonstrated a significant dose-dependent improvement in the mitochondrial function of BMMSCs obtained from ovariectomized rats (OVX-BMMSCs), as indicated by an elevation in mitochondrial membrane potential, adenosine triphosphate synthesis and expression of mitochondrial respiratory chain factors. Melatonin reduced the level of mitochondrial superoxide by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzymes, particularly superoxide dismutase 2 (SOD2). The protective effects of melatonin were found to be nullified upon silencing of Sirt1 or Sod2, underscoring the crucial role of the SIRT1-SOD2 axis in the melatonin-induced enhancement of mitochondrial energy metabolism in OVX-BMMSCs. To achieve a sustained and localized release of melatonin, silk fibroin scaffolds loaded with melatonin (SF@MT) were fabricated. The study involved the surgical creation of bilateral femur defects in OVX rats, followed by the implantation of SF@MT scaffolds. The results indicated that the application of melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of OVX-BMMSCs by reinstating mitochondrial redox homeostasis. These findings suggest that the localized administration of melatonin through bone implants holds potential as a therapeutic approach for addressing osteoporotic bone defects.

Diagnosing Osteoporosis in Diabetes-A Systematic Review on BMD and Fractures.

PURPOSE OF REVIEW: Recently, the American Diabetes Association updated the 2024 guidelines for Standards of Care in Diabetes and recommend that a T-score of - 2.0 in patients with diabetes should be interpreted as equivalent to - 2.5 in people without diabetes. We aimed to evaluate the most recent findings concerning the bone mineral density (BMD)-derived T-score and risk of fractures related to osteoporosis in subjects with diabetes. RECENT FINDINGS: The dual-energy X-ray absorptiometry (DXA) scan is the golden standard for evaluating BMD. The BMD-derived T-score is central to fracture prediction and signifies both diagnosis and treatment for osteoporosis. However, the increased fracture risk in diabetes is not sufficiently explained by the T-score, complicating the identification and management of fracture risk in these patients. Recent findings agree that subjects with type 2 diabetes (T2D) have a higher T-score and higher fracture risk compared with subjects without diabetes. However, the actual number of studies evaluating the direct association of higher fracture risk at higher T-score levels is scant. Some studies support the adjustment based on the 0.5 BMD T-score difference between subjects with T2D and subjects without diabetes. However, further data from longitudinal studies is warranted to validate if the T-score treatment threshold necessitates modification to prevent fractures in subjects with diabetes.