Prior Fracture Research Articles

Balancing fracture risk versus risk of mortality before fracture among women aged 80 years or older.

Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks. Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture. Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture. Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years.

The correlation between self-Hounsfield units and adjacent vertebral fracture after percutaneous vertebral augmentation: a retrospective cohort study.

Adjacent vertebral fracture (AVF) represents a prevalent and challenging complication after percutaneous vertebral augmentation (PVA) treatment for osteoporosis vertebral compressive fracture (OVCF). Lower bone mineral density (BMD) and intervertebral leakage are reportedly independent risk factors for AVF. Vertebral Hounsfield units (HU) measured from computed tomography (CT) scans can evaluate bone quality. This study sought to explore the risk factors associated with AVF and analyze the relationship between AVF and the Hounsfield units of adjacent vertebrae (self-HU) following PVA. In this retrospective cohort study, we included consecutive OVCF patients who presented to Xuzhou Central Hospital in Jiangsu Province, China from 1 January 2016, to 31 December 2019 for PVA treatment. Clinical and imaging data were collected, and baseline data were recorded. Patients were divided into the AVF group and the no-AVF group based on the presence of AVF during follow-up. Patients in the AVF group were further subdivided into the leakage group and the no-leakage group according to the presence of intervertebral leakage. Age, body mass index (BMI), fracture location, prior fracture, self-HU, and intervertebral leakage were included in univariate logistic regression analysis. Variables with a P value of less than 0.1 were then included in multivariate logistic regression analysis to determine the risk factors for AVF. Kaplan-Meier curves were plotted to assess the effect of intervertebral leakage on AVF using a log-rank test. A total of 460 patients were included in this study and followed up for an average of 50.9 months (range, 37-83 months). Among them, 82 cases (17.83%) developed AVF and were included in the AVF group. Multivariate logistic regression analysis showed that lower self-HU [odds ratio (OR) =0.972, 95% confidence interval (CI): 0.959-0.985, P<0.001] and intervertebral leakage (OR =2.618, 95% CI: 1.415-4.844, P=0.002) were risk factors for AVF following PVA. In the AVF group, 29 patients (35.37%) with intervertebral leakage were included in the leakage group. Patients in the leakage group had a shorter time to AVF (22.07±13.83 vs. 31.42±18.73, P=0.021) and higher self-HU (78.05±16.41 vs. 64.23±20.49, P=0.002) than those in the no-leakage group. Kaplan-Meier curves showed that the fracture-free time was shorter in the leakage group compared to the no-leakage group (log-rank test, P=0.014). Lower self-HU and intervertebral leakage are risk factors for AVF, and higher self-HU may lead to AVF when intervertebral leakage is present.

Shoulder Arthroplasty After Previous Nonarthroplasty Surgery: A Systematic Review and Meta-Analysis of Clinical Outcomes and Complications.

Many patients who undergo shoulder arthroplasty (SA) have had at least 1 nonarthroplasty shoulder surgery before the surgery. There is conflicting evidence regarding the effects of previous shoulder surgery on the outcome of SA. A systematic review was conducted to compare functional outcomes and complications between SA patients with and without prior non-SA surgery on the ipsilateral shoulder. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE/PubMed, Embase, Scopus, and Web of Science comprehensively from inception to January 2023. Based on 9,279 records reviewed, 26 comparative studies were included in the meta-analysis consisting of 5,431 shoulders with prior nonarthroplasty procedures (cases) and 55,144 shoulders without previous surgery (controls). Variables such as functional scores, complications, and range of motion were compared between cases and controls using Review Manager Software. In addition, subgroup analysis was conducted based on prior surgery type (rotator cuff repair [RCR], open reduction and internal fixation [ORIF], soft tissue repairs, and not specified) and type of SA (hemiarthroplasty, anatomical total shoulder arthroplasty, and reverse total shoulder arthroplasty [RTSA]). The results were presented as odds ratios (ORs) or standardized mean differences (SMDs). Except for a higher rate of periprosthetic joint infection (PJI) in patients who had undergone previous arthroscopic surgery (OR, 2.58; 95% confidence interval [CI], 1.66-4.01; p < 0.01), a higher rate of complications was only observed in patients with previous ORIF. These complications included aseptic loosening (OR, 3.43; 95% CI, 2.14-5.50; p < 0.01), shoulder dislocation (OR, 2.25; 95% CI, 1.05-4.84; p = 0.04), overall complication (OR, 3.95; 95% CI, 2.38-6.55; p < 0.01), and revision (OR, 2.52; 95% CI, 1.28-4.97; p = 0.01). Patients with a history of previous surgery demonstrated inferior functional outcomes in comparison with the control group, including American Shoulder and Elbow Surgeons (SMD, -0.39; 95% CI, -0.51 to -0.27; p < 0.01; I2 = 36%), Constant-Murley score (SMD, -0.34; 95% CI, -0.44 to -0.24; p < 0.01; I2 = 0%), abduction (SMD, -0.26; 95% CI, -0.45 to -0.08; p = 0.01; I2 = 54%), and flexion (SMD, -0.33; 95% CI, -0.46 to -0.21; p < 0.01; I2 = 40%). Subgroup analysis by previous type of surgery was not possible regarding functional outcomes. Patients who have had prior fracture surgery are at a higher risk of complications, reoperations, and revisions after SA than controls. The normal shoulder anatomy may be disrupted by prior surgery, which makes arthroplasty technically challenging, particularly when it comes to soft tissue balance. On the other hand, RCR before SA did not negatively affect clinical outcomes after RTSA and did not have a higher rate of overall complications (except PJI). Level III (Treatment Studies). See Instructions for Authors for a complete description of levels of evidence.

Pelvic Ring Fracture Management and Subsequent Pregnancy: A Summary of Current Literature.

The incidence of pelvic ring injuries is 34.3% per 100,000 capita. No studies have determined the ability of a female patient to have a vaginal delivery after undergoing pelvic fracture fixation. However, many obstetricians are generally unwilling to have their patients attempt a vaginal delivery in the setting of symphyseal or sacroiliac fixation. An exhaustive search of the National Library of Medicine database was performed, and it is hypothesized that cesarean section rates would be higher for women who have a child after one of these pelvic ring injuries. There is a 15% increase in cesarean rates using data from the National Center for Health Statistics. In addition, there is an observable increase in new cesarean rates. Currently, there is no clear evidence to support an elective cesarean section as the sole indication after a prior pelvic fracture. To date, no studies have determined the ability of a female patient to have a vaginal delivery after undergoing pelvic fracture fixation. Thus, until the increased cesarean section rate has been explained, it could be problematic to counsel the patient to avoid a vaginal delivery after sustaining a pelvic ring fracture. Hence, conducting additional studies on this topic would deem to be necessary.

Patient Self-Assessment of Walking Ability and Fracture Risk in Older Australian Adults

The relationship between self-reported walking limitation, a proxy of muscle function, and fracture risk has not been investigated. To examine the association between a self-reported walking limitation of 1000 m or less and 5-year risk of fracture. This prospective cohort study compared individuals with various degrees of walking ability limitation at 1000 m (a little limitation and a lot of limitation) and those without limitation (no limitation) accounting for age, falls, prior fractures, and weight. Participants from the ongoing population-based Sax Institute 45 and Up Study were followed from recruitment (2005-2008) for 5 years (2010-2013). Data analysis was conducted from July 2020 to September 2023. Self-reported walking limitation. Incident fracture and site-specific fractures (hip, vertebral, and nonhip nonvertebral [NHNV] fractures). Among the 266 912 participants enrolled in the 45 and Up Study, 238 969 were included, with 126 015 (53%) women (mean [SD] age, 63 [11] years) and 112 954 (47%) men (mean [SD] age, 61 [11] years). Approximately 20% reported a degree of limitation in walking 1000 m or less at baseline (39 324 women [24%]; 23 191 men [21%]). During a mean (SD) follow-up of 4.1 (0.8) years, 7190 women and 4267 men experienced an incident fracture. Compared with participants who reported no walking limitations, a little limitation and a lot of limitation were associated with higher risk of fracture (a little limitation among women: hazard ratio [HR], 1.32; 95% CI, 1.23-1.41; a little limitation among men: HR, 1.46; 95% CI, 1.34-1.60; a lot of limitation among women: HR, 1.60; 95% CI, 1.49-1.71; a lot of limitation among men: HR, 2.03; 95% CI, 1.86-2.22). Approximately 60% of fractures were attributable to walking limitation. The association was significant for hip, vertebral, and NHNV fracture and ranged between a 21% increase to a greater than 219% increase. In this cohort study of 238 969 participants, self-reported walking limitations were associated with increased risk of fracture. These findings suggest that walking ability should be sought by clinicians to identify high-risk candidates for further assessment.

Characterization and Predictors of Fractures following Hematopoietic Stem Cell Transplantation.

Bone loss and fractures are common and serious complications following hematopoietic stem cell transplantation (HSCT), and identifying risk predictors for fractures in transplant recipients remains challenging. The Taiwan Bone Marrow Donation Center is the largest databank of donors in Asia. However, no population-based studies have yet been conducted in Asia to accurately assess the risk of fractures. The aims of this study were to determine the incidence and risk factors for fractures in HSCT recipients. We conducted a retrospective cohort study of patients >18 years who received a HSCT from January 1, 2003 to September 30, 2015 using the Taiwan National Health Insurance Research Database. Fractures following HSCT were identified using ICD-9-CM codes. Cox regression analysis was used to identify risk factors for fractures. A total of 3327 patients underwent a HSCT, of whom 126 (3.8%) had a fracture after HSCT. The cumulative incidence of fractures was 5.3% at 5 years, and 10.8% at 10 years. Multivariate analysis showed that a fracture in the 3 years prior to transplant (HR = 3.79; 95% CI 2.39-6.03) was associated with a higher risk of fractures post HSCT. With a daily dose equivalent of >0.50-3.75 mg, >3.75-15.23 mg and >15.23 mg prednisolone, the risk of fractures increased by 1.70 (95% CI 1.07-2.71), 2.23 (95% CI 1.32-3.76) and 2.93 (95% CI 1.43-6.01) folds, respectively. Regular screening to monitor bone loss should be initiated early, and counseling about the importance of general preventive measures for bone loss is warranted in HSCT recipients with a prior fracture and mean daily dose of steroids >0.50 mg.

Sex Difference in the Association between Prior Fracture and Subsequent Risk of Incident Dementia: A Longitudinal Cohort Study.

A history of fracture has been associated with increased risk of dementia; however, it is uncertain whether sex difference exists in the association between prior fracture and subsequent risk of incident dementia. To investigate whether sex modified the relationship between prior fracture and subsequent risk of dementia. Prospective cohort study. UK Biobank. 496,331 participants (54.6% women) free of dementia at baseline. History of fracture was self-reported via touchscreen questionnaires at baseline. The primary outcome was all-cause dementia. Both any fracture and fragility fracture were significantly associated with an increased risk of subsequent all-cause dementia in men (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.14-1.43; adjusted HR: 1.48; 95% CI: 1.18-1.87, respectively), but not in women (adjusted HR: 1.04; 95% CI 0.95-1.15; adjusted HR: 1.01; 95% CI: 0.87-1.18, respectively); and these sex-differences were significant (P interaction = 0.006; P interaction = 0.007, respectively). The sex differences in the impacts of different fracture sites (including upper limb, lower limb, spine, and multiple sites) were consistent on all-cause dementia. This study demonstrated that prior fracture was associated with an increased risk of dementia in men but not in women, and the sex difference was significant. Previous fracture may be an important marker for identifying subsequent dementia in middle-aged and older men.

Amenorrhea and Stress Fractures in Female New Jersey Division III Collegiate Runners: An Opportunity for Increased Health Education

BACKGROUND: In the National Collegiate Athletic Association (NCAA), 9.1% of the injuries reported by women’s cross-country athletes between 2014-2019 were fractures. Both history of amenorrhea and prior stress fractures have been found to predict incidence of subsequent bone stress injuries among female athletes. Although excessive exercise is a major contributor to the development of amenorrhea, there are currently no studies on the association between amenorrhea and stress fractures in New Jersey (NJ) National NCAA Division III Women’s cross country or track athletes. This study aims to determine if there is an association between incidence of amenorrhea and subsequent occurrence of stress fractures among this population, and to identify a possible area for increased reproductive health education. METHODS: This is a survey-based study. Participants were female athletes over the age of 18 who currently participate in collegiate cross country or track running at a NJ Division III school. Coaches of the Division III cross country and track teams in NJ distributed a survey to their female athletes to gain participants for this study. Survey data included information on participant menstrual history, stress fracture history, and athletic involvement. Participants also indicated if their school’s staff had ever educated them on the importance of menstrual regularity and athletics. Descriptive statistics and comparison between groups were analyzed. RESULTS: In total, 68 survey responses were collected. Survey respondents included female NJ cross country and track athletes ages 18-23, from a total of eight institutions. During training or competition, 58.8% of the study participants missed at least one menstrual cycle and 45.6% experienced a stress fracture. There is a significant association between having missed at least one menstrual cycle during training or competition and the number of stress fractures experienced by the athlete (p = 0.044). Only 30.9% of respondents indicated that someone from their school’s staff spoke to them about the importance of maintaining regular menstruation during training. CONCLUSION: This study confirms that both amenorrhea and stress fractures are commonly seen among NJ NCAA Division III female cross country and track athletes. Our data also highlights a need for increased education of NJ Division III female athletes regarding the importance of maintaining regular menstruation as a means of stress fracture prevention. Further investigation of the role of amenorrhea on the incidence of stress fractures may shine light on an important area for prevention and increased health education.

Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan.

This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs. We used data from the National Database of Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index. We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65-74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval [CI], 0.98-1.03) for bisphosphonates, 0.46 (95% CI, 0.44-0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18-0.32) for estrogens, 0.75 (95% CI, 0.71-0.79) for calcitonins, and 0.93 (95% CI, 0.84-1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14-1.22). The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.

Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems.

Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. Retrospective analyses of electronic health record data from 3 US integrated health care systems. Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.

Total Hip Arthroplasty Following Operative Fixation of Acetabular Fracture: A Contemporary Series

BackgroundTotal hip arthroplasty (THA) is the operation of choice for salvage of post-traumatic arthritis following acetabular fracture. While high failure rates have been reported for these procedures, existing literature reports mainly on historical implant designs and techniques. We aimed to describe implant survivorships, complications, radiographic results, and clinical outcomes of contemporary THA following prior open reduction internal fixation (ORIF) of an acetabular fracture. MethodsWe identified 104 patients undergoing THA following prior ORIF of an acetabular fracture from 2000 to 2015 via our institutional total joint registry. Mean age at THA was 50 years (range, 18 to 79 years), 71% were men, and mean body mass index was 27 (range, 18 to 52). All patients were implanted with uncemented acetabular components, and 89% had uncemented stems. Some hardware from prior fixation was retained in 94% of cases. Mean follow-up was 10 years (range, 2 to 21 years). ResultsThe 10-year survivorships free of any revision and any reoperation were 98% and 97%, respectively. There were 4 revisions: 1 each for psoas tendonitis, dislocation, acetabular aseptic loosening, and periprosthetic joint infection. There were 9 complications that did not lead to reoperation: 5 dislocations, 2 periprosthetic femur fractures, 1 sciatic nerve palsy, and 1 case of symptomatic heterotopic ossification. All unrevised components appeared radiographically well-fixed. Mean Harris Hip Score improved from mean 50 preoperatively to mean 82 at 5 years (P < .001). ConclusionsIn this series of contemporary THAs following prior acetabular fracture ORIF, revision-free survivorship was excellent with only a single case of acetabular aseptic loosening. These results are encouraging and suggest that contemporary implants and techniques have notably improved on historic results. Level of EvidenceTherapeutic, Level IV.

Osteoporosis in Renal Disease.

Osteoporosis is a disorder characterized by decreased bone mass and skeletal fragility with increased fracture risk. Chronic kidney disease presents with wide range of bone metabolic disorders, including osteoporosis. Osteoporosis prevalence is high in early stages of CKD; whereas in late stages, it coexists with renal osteodystrophy. Risk factors for osteoporosis include advancing age, low bone mineral density (BMD), glucocorticoid therapy, smoking, alcohol intake, etc. The diagnosis of osteoporosis in renal disease is made after assessment of BMD, in addition to exclusion of chronic kidney disease-mineral bone disorder (CKD-MBD), eliciting history of prior fragility fractures and relevant laboratory investigations. The treatment of osteoporosis varies with the different stages of CKD, with management in stages 1-3 being similar to the general population. Special emphasis must be laid on prevention of fractures as well.

Osteogenesis Stimulator Devices Reduce Surgical Intervention, Opioid Utilization, and Overall Costs in Patients with Fracture Nonunions.

Approximately 10% of fractures result in delayed union or nonunion. These cases result in pain and disability as well as increased utilization of healthcare resources such as pain medication, physical therapy, and subsequent surgery. Osteogenesis stimulator devices are a safe and low-cost, non-invasive option to aid healing in nonunion cases. Study objectives aimed to evaluate real-world data of osteogenesis stimulator device usage in a variety of healthcare utilization endpoints including surgical intervention for nonunion, pain medication use, and overall healthcare costs. Data were stratified into three groups: the Stim Device group and the No Stim and Surgical control groups. A retrospective analysis of a large claims-based database was conducted. The database was queried for adult patients having a diagnosis of nonunion, with evidence of a prior fracture in the previous 180 days (n = 11,010). The osteogenesis stimulator group (Stim Device group, n = 1,628) was defined as those patients having at least one claim for an osteogenesis stimulator in the period 90 to 180 days following fracture and up to 60 days following the nonunion diagnosis. The control group (No Stim group, n = 9,382) had a nonunion diagnosis with evidence of a fracture in the prior 180 days but did not receive a device. A total of 1,751 patients from the No Stim group were sub-grouped into surgical/operative controls (No Stim - Surgical group). Stim Device patients showed lower rates of surgical intervention for their bone nonunion compared to the No Stim patients (214/1,628, 13.1% vs.1,751/9,382, 18.7%, p < 0.001). Stim Device patients had lower rates of opioid utilization post-index compared to No Stim patients (948/1,628, 58.2% vs.6,359/9,382, 67.8%, p < 0.001). Overall healthcare costs were significantly reduced in the Stim Device group ($21,654) compared with No Stim ($29,101; p < 0.001) and Surgical ($35,914; p < 0.001) control groups. The results show that bone growth stimulator devices have a positive individual and societal impact on treating patients with fracture nonunions.

Intramedullary implant stability affects patterns of fracture healing in mice with morphologically different bone phenotypes

Almost all prior mouse fracture healing models have used needles or K-wires for fixation, unwittingly providing inadequate mechanical stability during the healing process. Our contention is that the reported outcomes have predominantly reflected this instability, rather than the impact of diverse biological conditions, pharmacologic interventions, exogenous growth factors, or genetic considerations. This important issue becomes obvious upon a critical review of the literature. Therefore, the primary aim of this study was to demonstrate the significance of mouse-specific implants designed to provide both axial and torsional stability (Screw and IM Nail) compared to conventional pins (Needle and K-wires), even when used in mice with differently sized marrow canals and diverse genetic backgrounds. B6 (large medullary canal), DBA, and C3H (smaller medullary canals) mice were employed, all of which have different bone morphologies. Closed femoral fractures were created and stabilized with intramedullary implants that provide different mechanical conditions during the healing process. The most important finding of this study was that appropriately designed mouse-specific implants, providing both axial and torsional stability, had the greatest influence on bone healing outcomes regardless of the different bone morphologies encountered. For instance, unstable implants in the B6 strain (largest medullary canal) resulted in significantly greater callus, with a fracture region mainly comprising trabecular bone along with the presence of cartilage 28 days after surgery. The DBA and C3H strains (with smaller medullary canals) instead formed significantly less callus, and only had a small amount of intracortical trabeculation remaining. Moreover, with more stable fracture fixation a higher BV/TV was observed and cortices were largely restored to their original dimensions and structure, indicating an accelerated healing and remodeling process. These observations reveal that the diaphyseal cortical thickness, influenced by the genetic background of each strain, played a pivotal role in determining the amount of bone formation in response to the fracture. These findings are highly important, indicating the rate and type of tissue formed is a direct result of mechanical instability, and this most likely would mask the true contribution of the tested genes, genetic backgrounds, or various therapeutic agents administered during the bone healing process.

Using Risk Scores to Estimate Lower Extremity Fragility Fracture Risk among Individuals with Chronic Spinal Cord Injury: A Preliminary Model.

To develop SCI-FX, a risk score to estimate 5-year lower extremity fragility fracture risk among patients living with chronic spinal cord injury (cSCI). Adults with traumatic cSCI (n = 90) participated in a 2-year prospective longitudinal cohort study describing bone mineral density (BMD) change and fracture incidence conducted at the Lyndhurst Centre (University Health Network), University of Waterloo, and Physical Disability Rehabilitation Institute of Québec City. Prior publication and clinical intuition were used to identify fragility fracture risk factors including prior fragility fracture, years post-injury, motor complete injury (AIS A/B), benzodiazepine use, opioid use, and parental osteoporosis. We conducted bivariate analyses to identify variables associated with fracture. Multiple logistic regressions were performed using fragility fracture incidence as the dependent variable and all variables from the univariate analyses with a highly liberal p value at 0.2. Using the odds ratios (ORs) from the multiple logistic regression model, a point system for fragility fracture risk score was developed, and the odds of fracture for each point was estimated. All initial variables, with the exception of benzodiazepine exposure, were included in the final model. We identified a simple preliminary model for clinicians to estimate 5-year fracture risk among patients with cSCI based on their total score.

Prior Fragility Fractures are Associated With a Higher Risk of Bone Health-Related Complications Within Eight Years Following Lumbar Fusion.

Retrospective study. To determine the 8-year risk of revision lumbar fusion, pseudoarthrosis, mechanical failure, fragility fracture, and vertebral compression fracture in patients with a prior fragility fracture compared with those without. Osteoporosis is a known modifiable risk factor for revision following lumbar fusion due to inadequate fixation. Patients with prior fragility fractures have been shown to have increased bone health-related complications following various orthopedic surgeries; however, there is a paucity of literature that identifies these complications in patients undergoing lumbar fusion. Patients aged 50 years and older who underwent elective lumbar fusion were identified in a large national database and stratified based on whether they sustained a fragility fracture within three years prior to fusion. These patients were propensity-score matched to a control based on age, gender, and Charlson the comorbidity index using a 1:1 ratio. Kaplan-Meier and Cox proportional hazards analyses were used to observe the cumulative incidences and risk of complications within eight years of index surgery. After matching, 8805 patients were included in both cohorts. Patients who sustained a prior fragility fracture had a higher risk of revision [hazard ratio (HR): 1.46; 95% CI: 1.26-1.69; P <0.001), pseudoarthrosis (HR: 1.31; 95% CI: 1.17-1.48; P <0.001), mechanical failure (HR: 2.08; 95% CI: 1.78-2.45; P <0.001), secondary fragility fracture (HR: 6.36; 95% CI: 5.86-6.90; P <0.001), and vertebral compression fracture (HR: 7.47; 95% CI: 7.68-8.21; P <0.001) when compared with the control cohort. Patients who sustain a fragility fracture prior to lumbar fusion have an increased risk of revision, pseudoarthrosis, and mechanical failure within eight years. Surgeons should be aware of this high-risk patient population and consider bone health screening and treatment to reduce these preventable complications.

Prevention of Hip Fractures: Trade-off between Minor Benefits to Individuals and Large Benefits to the Community.

Goeffrey Rose postulated that a population-based measure bringing a small benefit to each individual can yield large benefits to the community. We aimed to test this axiom by quantifying the relationship between change in bone mineral density (BMD) and hip fracture incidence between two prospective cohorts separated by ~10 years. In this prospective population-based Dubbo Osteoporosis Epidemiology Study (DOES), the participants aged 60+ were recruited in two waves: the initial cohort (1311 women, 842 men) in 1989 to 1992 and the second cohort (974 women, 544 men) in 1999 to 2001. The incident hip fracture was radiologically ascertained. Femoral neck BMD was measured biannually. Multivariable-adjusted Cox's proportional hazards models were adjusted for the predefined covariates such as age, BMI, lifestyle factors, falls, and prior fracture. Compared with the initial cohort, the second cohort had a higher femoral neck BMD by ~0.04 g/cm2 in women and 0.03 g/cm2 in men. However, the prevalence of osteoporosis in the second cohort was halved (prevalence ratio 0.51, 95% CI 0.36 to 0.73 in women; 0.45, 0.24 to 0.84 in men), and its hip fracture incidence was significantly reduced (hazard ratio 0.54, 95% CI, 0.38 to 0.78 in women; 0.39, 0.19 to 0.80 in men). Sensitivity analyses indicated that the "effect" was unlikely due to unmeasured confounders. These findings suggest that a population-wide strategy aimed at enhancing BMD across the entire population could lead to a substantial decrease in the incidence of hip fractures. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

THU466 XLH During Pregnancy: A Closer Look Based On Real-World Experience

Abstract Disclosure: D.S. Ali: None. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx. Background: X-linked hypophosphatemia (XLH) is a genetic disorder caused by mutation in the PHEX gene leading to excess serum levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23). High FGF23 causes renal phosphate wasting, decreased production of serum 1,25-dihydroxy vitamin D, and increased metabolism of 1,25-dihydroxy vitamin D, leading to hypophosphatemia. Maintaining normal serum phosphorus levels in pregnant women with XLH is critically important to ensure mineralization of the fetal skeleton. Multiple factors may influence phosphorus homeostasis in pregnancy, including an increase in PTHrP production and a tripling of calcitriol beginning in the first trimester. Case study: 30 years old Gravida 1 Para 0 with XLH, diagnosed at the age of 18 months. She has a pathogenic heterozygous mutation of the PHEX gene (c.1645+1G&amp;gt;A). Treated with phosphate and calcitriol since diagnosis. Had no history of neonatal seizure or respiratory distress, and no dental or renal manifestations. No prior fractures or corrective surgeries and has a normal BMD. No history of enthesopathy, however, has chronic joint pain &amp;gt; 1 year. The pregnancy progressed well with no issues; the patient chose not to undergo amniocentesis for fetal diagnosis. She was monitored closely every 3 weeks, aiming to maintain the serum phosphorus within the normal range to ensure adequate mineralization of the fetal skeleton. The requirements for phosphate increased by 50% in the 2nd trimester and by 125% in the 3rd trimester compared to baseline. While the calcitriol dose increased by 25% in the 3 trimesters compared to baseline. Because further increases in the calcitriol dose were associated with hypercalciuria, the dose was carefully titrated. The mean serum phosphorus level was maintained in the low normal reference range at 0.79 - 0.8 mmol/L (NR: 0.8-1.45), mean TmP/GFR 0.611 (NR: 0.96-1.44). She was induced at 37 weeks due to cholestasis, and delivered with a vaginal delivery. The baby boy weighed 2.690 kg and had slightly low serum phosphorus and calcium levels at birth, which corrected spontaneously. DNA analysis confirmed that the baby also has a pathogenic mutation of the PHEX gene. Conclusion: There was a noticeable variation in the serum phosphorus levels during the 1st and 2nd trimesters and less so in the 3rd trimester and during lactation. The dose of phosphate and active vitamin D required careful upward titration to maintain a normal serum phosphorus level. Therefore, close monitoring is essential. Although the rate of c-sections is higher (76%) amongst the XLH patient population compared to the normal population 27.1%, our patient delivered vaginally with no adverse skeletal outcomes in the mother or neonate. Presentation: Thursday, June 15, 2023

OR13-06 Romosozumab After Denosumab Improves Lumbar Spine Bone Mineral Density And Microarchitecture Greater Than Denosumab Continuation In Postmenopausal Women

Abstract Disclosure: N. Hong: None. S. Shin: None. H. Kim: None. Y. Rhee: None. Transitioning to romosozumab from antiresorptives can be an effective strategy to improve bone strength. A phase 2 trial and a few observational studies showed improvement of lumbar spine bone mineral density (BMD) with maintained hip bone density by romosozumab after denosumab. However, whether transition to romosozumab after denosumab is associated with greater improvement in BMD and microarchitecture compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020 (at least two injections; n=696). Individuals who were transited to 12 months of romosozumab after denosumab (n=105) were 1:1 matched to those who continued denosumab (n=591) by propensity score using age (69 years), body mass index, BMD, and numbers of denosumab injection at the time of transition, BMD improvement during denosumab treatment, prior fracture and bisphosphonate use (n=93 for each; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). BMD gain by denosumab in DR and DD groups from denosumab initiation to transition time (to romosozumab or denosumab continuation; median 4 times [range 2 to 8] of denosumab injection) was +4.6% and +2.4% in the lumbar spine (LS, T-score −3.4 to −3.1) and total hip (TH, T-score −2.5 to −2.4), without statistical difference. DR group showed greater LSBMD gain compared to the DD (+7.0% vs. +2.5%, P&amp;lt;0.001) during 12 months after the transition time, yielding greater net LSBMD gain in DR (median 2 years of denosumab followed by 1-year romosozumab) compared to DD (median 3 years of denosumab; +11.6% vs. +7.0%, P&amp;lt;0.001). Differences in LSBMD gain between DR and DD groups remained robust (adjusted difference +4.7% point, P&amp;lt;0.001) after adjustment for covariates. Hip BMD changes did not differ between DR and DD (DR vs. DD; FN, +1.3% vs. +2.0%, p=0.409; TH, -0.9% vs. +0.2%, P=0.132). DR group showed significant improvement in the trabecular bone score during romosozumab use (1.288 to 1.311, p=0.005), whereas denosumab continuation in the DD group did not (1.297 to 1.309, p=0.103). During 12 months, one incident morphometric vertebral fracture (grade 1) and one nonvertebral fracture (patella) were observed in DD, whereas one ankle fracture was observed in the DR group. In summary, romosozumab after denosumab improved lumbar spine BMD and microarchitecture greater than denosumab continuation, with the maintenance of hip BMD. Presentation: Friday, June 16, 2023

FRI675 Higher FSH Level Is Associated With Increased Risk Of Incident Hip Fracture In Older Adults, Independent Of Sex Hormone Levels

Abstract Disclosure: E.H. Koh: None. S.K. Ewing: None. S. Sigurdsson: None. V. Guðnason: None. T.F. Hue: None. E. Vittinghoff: None. M. Zaidi: Research Investigator; Self; patents on FSH, bone, body fat and neurodegeneration. Held by Icahn School of Medicine and Mount Sinai. C.J. Rosen: None. C. Ohlsson: None. L. Grahnemo: None. Å. Tivesten: None. A.V. Schwartz: None. A.L. Schafer: None. Higher levels of follicle stimulating hormone (FSH) are associated with bone loss among women during the perimenopausal transition and among older men, independent of sex hormone levels. In vitro studies have shown bone remodeling via FSH-receptors on bone cells. Furthermore, treating ovariectomized mice with FSH-blocking polyclonal antibodies results in increased bone mineral density. However, it is uncertain whether this association of FSH elevation and bone loss translates to increased fracture risk. To examine the relationship between FSH and incident hip fracture, independent of sex hormone levels, we used a case-cohort design to sample from the AGES-Reykjavik cohort, a longitudinal cohort of 5764 older Icelandic adults designed to assess gene/environment interactions and their relationship to diseases in old age. Baseline visits took place from 2002 and through 2006. We excluded those with prior hip fracture, those whose quantitative computed tomography bone mineral density scan quality was unacceptable, or who were taking sex hormone replacement, sex hormone antagonists, or glucocorticoid medications. We randomly sampled, stratified by sex, 147 women and 148 men to form our subcohort. Our cases were comprised of a random sample, stratified by sex, of 133 women and 122 men (of whom 25 were in the subcohort) who sustained incident hip fracture within 10 years of the baseline visit. Fractures were adjudicated and recorded in the AGES-Reykjavik fracture registry. FSH and sex hormone binding globulin (SHBG) were measured on baseline serum by immunoassay and estradiol and total testosterone by mass spectrometry. Robust weighted Cox proportional hazards models were used to determine the relationship between FSH and subsequent risk of hip fracture, with adjustment for covariates. Among the subcohort, mean age was 76 years. In women, mean ± SD FSH was 64.4 ± 25.5 IU/L with estradiol 5.7 ± 4.2 pg/mL, testosterone 22.5 ± 10.4 ng/dL, and SHBG 74.0 ± 33.8 nmol/L. In men, mean FSH was 12.2 ± 11.9 IU/L with estradiol 21.3 ± 6.9 pg/mL, testosterone 457.9 ± 171.2 ng/dL, and SHBG 52.8 ± 17.5 nmol/L. No interaction was identified between FSH and sex for the relationship with fracture, so men and women were pooled for analysis. Higher levels of FSH were associated with a significant increased risk of incident hip fracture in models adjusted for age and sex [hazard ratio (HR) 1.24 (95% CI 1.04-1.48, p=0.02)] and after further adjustment for estradiol, testosterone, and SHBG levels [HR 1.20 (95% 1.01-1.44, p=0.04)] per sex-specific SD increase in FSH level. Our findings support a growing body of evidence for direct pleiotropic effects of FSH on bone. FSH may contribute to aging and disability independent of sex hormone levels. Presentation: Friday, June 16, 2023