Fracture Risk Research Articles

Decreased trabecular bone score in patients affected by Fabry disease.

Fabry disease (FD) is an inherited X-linked lysosomal storage disease characterized by increased risk of osteoporosis and fractures. The impact of FD on clinical measures of bone quality is unknown. This considered, aim of our study was to evaluate whether trabecular bone microarchitecture, measured by trabecular bone score (TBS), is altered in patients with FD compared to control subjects. This retrospective monocentric study enrolled 14 patients (M/F 1/1, median age 46 [37-63] years, range 31-72 years) newly diagnosed with FD between January 2016 and July 2023 who underwent dual-energy X-ray absorptiometry (DXA) image at the time of diagnosis and 42 matched controls. In all subjects, data about bone mineral density (BMD) and lumbar spine TBS were collected and total calcium, parathyroid hormone (PTH), 25(OH) vitamin D, alkaline phosphatase (ALP), creatinine and estimated glomerular filtration rate (eGFR) were evaluated. In subjects with FD, globotriaosylsphingosine (lyso-Gb3), 24-hour proteinuria and albumin-creatinine ratio were also assessed. Patients with FD presented significantly lower lumbar spine TBS (1.29 [1.22-1.38] vs. 1.42 [1.39-1.47], p < 0.001) and lower lumbar spine BMD (0.916 ± 0.166 vs. 1.031 ± 0.125g/cm2, p = 0.008) compared to controls; moreover, FD was shown to be an independent risk factor for both low lumbar spine TBS (β = -0.118, p < 0.001) and BMD (β = -0.115, p = 0.009). No differences were found in serum calcium, ALP, 25(OH) vitamin D and eGFR in both groups, but FD patients had significantly higher PTH levels compared to controls (p = 0.016). Finally, 8 patients with FD presented either moderately or severely increased albuminuria and only 2 patients presented normal lyso-Gb3 levels. Patients affected by FD present significantly lower lumbar spine TBS and BMD compared to controls. Our findings strongly support the importance of carrying out a thorough evaluation of bone status in all patients affected by FD at baseline.

Bilateral atypical femur fracture in a patient with breast cancer taking zoledronic acid and denosumab: a case report.

A 54-year-old woman developed stage IV breast cancer 8 years prior. Chemotherapy was administered, and she was started on zoledronic acid treatment for her bone metastases. Her chemotherapy regimen was then switched, owing to disease progression. Fifty-seven months after starting treatment with zoledronic acid, the patient suffered an atypical femoral fracture of her right femur, for which she underwent surgery. Twenty months later, she developed another atypical femoral fracture in her left femur and underwent intramedullary nail fixation. Zoledronic acid and denosumab use in patients with metastatic bone tumors caused by breast cancer should be done cautiously, considering atypical femoral fracture risk.

Screening for endogenous hypercortisolism in patients with osteoporosis and fractures: why, when and how.

Skeletal comorbidities are frequent and clinically relevant findings in Cushing's syndrome (CS) since an uncoupled suppressed bone formation and enhanced bone resorption leads to a marked skeletal damage with a rapid increase of fracture risk. Reduced Bone Mineral Density (BMD) has been consistently reported and osteopenia or osteoporosis are typical findings in patients with CS. Vertebral Fractures (VFs) are frequently reported and may occur even in patients with an only mild reduction of BMD. Since CS is diagnosed late due to often difficult biochemical and radiological confirmation as well as to signs and symptoms common in other much more frequent diseases an approach suggested for overcoming underdiagnosis is to screen patients with manifestations which may overlap with those of CS such as arterial hypertension, diabetes mellitus and osteoporosis. Our review will focus on the rationale and best practice for screening osteoporotic patients for CS.

Osteoporosis in older men

Osteoporosis, characterized by reduced bone mass and compromised skeletal microarchitecture, significantly increases the risk of fractures and is the most prevalent metabolic bone disease. While it is commonly associated with post-menopausal women, osteoporosis and subsequent fractures are also substantial concerns in men. Men experience sustained bone loss after the sixth decade, with estimates indicating that 20% of Americans with osteopenia or osteoporosis are men. Approximately one in eight men over 50 will suffer an osteoporotic fracture, with hip fractures in men leading to a two- to threefold increase in mortality compared to women. The prevalence of osteoporosis in men has risen, doubling in prevalence since the early 1990s. Men generally have higher peak bone mass and greater bone size, offering some protection against osteoporosis; however, aging leads to increased bone resorption and decreased bone formation, exacerbated by lower androgen and estrogen levels. Secondary causes, such as hypogonadism and chronic glucocorticoid use, are prevalent in men. Diagnosis primarily involves bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA), with fracture risk assessment tools like FRAX and MORES aiding in clinical decisions. Treatment includes calcium and vitamin D supplementation, bisphosphonates, denosumab, and anabolic agents like teriparatide and abaloparatide. Special considerations are necessary for men undergoing androgen deprivation therapy for prostate cancer due to accelerated bone loss. Effective management requires early diagnosis, lifestyle modifications, and appropriate pharmacological interventions to reduce fracture risk and improve patient outcomes.

Between a Rock and a Short Place-The Impact of Nephrolithiasis on Skeletal Growth and Development Across the Lifespan.

The impact of nephrolithiasis on skeletal growth and bone health across the life span of kidney stone formers is reviewed. Bone disease is an early event among kidney stone formers (SF), with distinct phenotypes according to each age, sex, menopausal status, dietary, hormonal and genetic factors. Nephrolithiasis-associated bone disorder is characterized by reduced bone mineral density (BMD) and histologically discloses low bone formation, high bone resorption and abnormal mineralization. Although hypercalciuria has been presumed to be pathogenic for bone loss in SF, the association of BMD with urinary calcium is not uniform in all studies. Hypocitraturia, metabolic disturbances, cytokines and receptors, growth factors and acid-base status may all influence skeletal outcomes. The potential link of bone disease with vascular calcification and cardiovascular disease among SF is discussed. The unique vulnerability of the younger skeleton to the effects of nephrolithiasis on attainment of peak bone mass and strength is highlighted and the association of bone loss with kidney stone formation early in life indicate the opportunity for intervention to reduce the risk of future bone fractures.

Rationale and Protocol of the ETERNITY-ITA Study: Use of Etelcalcetide for Preserving Vitamin K-Dependent Protein Activity—An Italian Study

Background/Objectives: Chronic kidney disease and mineral bone disorders (CKD-MBD) are frequently associated with an increased risk of both vascular calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and bone Gla protein (BGP), have pivotal roles both for VCs and BFs. The VIKI study highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs beyond the beneficial effect of reducing PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age- and sex-matched patients treated with calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on an individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusions: This study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively.

The association between fracture and short-term adverse health outcomes among children with cerebral palsy

BackgroundChildren with cerebral palsy (CP) have a high risk of fracture; yet, little is known about their post-fracture health outcomes. A fracture is an unplanned event in contrast to surgeries or procedures where there is a pre-operative period to optimize body composition and health and planned post-operative follow-up care. Fractures may be associated with significant outcomes due to the unplannable nature and reactionary care. The objective of this study was to determine if fractures were associated with an increased rate of short-term adverse health outcomes among children with CP, and if these associations were dependent on age. MethodsThis retrospective cohort study used commercial claims from 01/01/2001–12/31/2018. The primary cohort was children 2–18 years old with CP and an incident fracture (CP + Fx). Comparison cohorts were propensity score matched 1:1 to CP + Fx on demographic and health-related indicators: CP without fractures (CPw/oFx); without CP with (w/oCP + Fx) or without (w/oCPw/oFx) a fracture. The incidence rate (IR) and IR ratios (IRR) of 30-day and 31–90-day pneumonia and 90-day emergency department (ED) visit were estimated. Cox regression tested for effect modification by age and sex. ResultsThe CP + Fx cohort (n = 1670) had higher IRs of 30-day pneumonia (IRR range, 1.53–4.54) and 90-day ED visit (IRR range, 1.45–2.37) (all P < 0.05), and higher IRs of 31–90-day pneumonia but this did not reach statistical significance (IRR, 1.41 to 2.32, all P > 0.05). Notably, there was evidence of effect modification by age. The rate of 30-day pneumonia became more problematic for CP + Fx with older age relative to comparison cohorts and for 90-day ED visit compared to CPw/oFx. The rate of 90-day ED visit for CP + Fx was more problematic at younger ages compared to w/oCP + Fx. ConclusionsFractures among children with CP were associated with an increased rate of short-term pneumonia and ED visit, which was more problematic with older age.

Features of the state of bone tissue in children with cerebral palsy. Part 1. Etiological aspects. A literature review

BACKGROUND: The growth of the human body is the most significant period of development of the bone tissue, because it is during this period that the size, shape, and architectonics of bone are formed against the background of increasing body weight and increasing physical exertion. Considering a number of pathological factors of the underlying disease (alimentary, neurological, hormonal, stress, and physical), bone tissue in children with cerebral palsy grows and develops with deviations from the norm. АIM: To present up-to-date generalized information about the features of bone tissue in children with cerebral palsy to orthopedic traumatologists, neurologists, and physical therapy specialists. MATERIALS AND METHODS: Studies on the problem of bone tissue condition in patients with cerebral palsy were analyzed. Data published over the past 20 years were searched in the scientific databases PubMed, Google Scholar, Cochrane Library, Crossref, and eLibrary without language restrictions. RESULTS: In the last 20 years, the number of studies about pediatric osteoporosis has increased. The gold standard for determining the level of bone mineral density is dual-energy X-ray absorptiometry. However, its use in children has presented some difficulties and limitations. In children, the relationship between bone mineral density values and the risk of fractures has not been well studied, which does not allow us to discuss about osteoporosis based on densitometric bone mineral density data alone. In patients with cerebral palsy, a decrease in bone mineral density and bone mass during growth was found. Previous studies showed that the main factors associated with a decrease in bone mineral density in this group of patients include neuroendocrine causes due to growth retardation against the background of CNS damage, alimentary factors, decreased calcium and vitamin D concentrations, systemic use of glucocorticoids, intake of antiepileptic drugs, decreased motor activity, and low muscle mass. Increasing serum vitamin D concentrations does not have a positive effect on bone mass, although increasing serum calcium concentrations is associated with an increase in bone mineral density. CONCLUSIONS: Identifying and correcting factors leading to decreased bone mineral density in children with cerebral palsy can improve bone health in this group of patients. The absence of a relationship between bone mineral density values and the risk of fractures in children with cerebral palsy does not allow us to discuss about osteoporosis based only on bone mineral density densitometric data. There may be more factors leading to an increased risk of bone fractures in children with cerebral palsy that require further study.

Finite element analysis confirms the optimal apex position in medial opening wedge high tibial osteotomy to avoid lateral hinge fracture.

Lateral hinge fracture is a significant complication of medial opening wedge high tibial osteotomy. While fracture risk is closely associated with the osteotomy apex position, the optimum position remains variable within the literature. Our hypothesis is that stresses at the osteotomy apex predicted by finite element analysis can be used to identify an apex position which minimises intra and postoperative fracture risks. A finite element model was studied to investigate the effect of varying the hinge position on fracture risk and severity for a given bone geometry; variables analysed included stress, strain and micromotion levels. Nine further knee models were studied to assess the variability between patients' bone properties and examine the effect of apex location on strains. Lateral hinge width and height significantly influence intra-operative stress, strain, and fracture risk, while hinge width predominately determines postoperative stability. Wider hinges improve postoperative stability, but increase the likelihood of intra-articular fractures. Aiming the apex at the fibular head height minimises strain. The osteotomy apex should be located such that the hinge width is equal to 13% of the medial-lateral width to minimise apex stress and fracture risk while preserving sufficient bone at the hinge for stability. The height of the apex from the tibial plateau should maintain a minimum value of 16% of the medial-lateral width to avoid intra-articular fracture, with the apex below the fibula head if necessary. The size of the tibia does not alter the optimal location, making our findings applicable across all tibia sizes. Our study has investigated and verified a proposed optimal apex position, based upon fracture risk prediction and micromotion at the osteotomy apex. This is clinically useful due to the potential use of the apex point on preoperative 2D radiographs when planning surgery. Not applicable.

Individuals with a fragility fracture and a prescription for bone active medication have a positive perception of the medication but do not associate it with fracture risk reduction.

Our purpose was to examine perceptions about bone active medication from individuals with a fragility fracture and a prescription for bone active medication. In this qualitative description study, eligible participants were those who attended an Osteoporosis Canada education session, and reported sustaining a previous fragility fracture and receiving a prescription for bone active medication. We conducted one-on-one interviews and analyzed the data using the analytic hierarchy approach. We interviewed 32 female participants (age range 58-89years). Based on our analysis, two themes were developed: (1) most participants spoke positively about bone active medication, indicating they were willing to start, or continue to take, their medication. Positive perceptions were held by participants who sustained a fracture while taking bone active medication, participants whose healthcare provider had stopped the prescription, and participants who reported side effects from the medication; (2) most participants did not discuss bone activemedication in relation to their fracture and did not appear to connect the medication to the concept of fracture risk. Instead, participants talked about themedication in relation to bone health in general, or to bone density. Participants appeared to have positive perceptions of bone active medication, despite sustaining a fracture while taking the medication, reporting medication side effects, or having a healthcare provider stop the prescription. Participants did not connect bone active medication to the concept of fracture risk, illustrating the need for healthcare providers to emphasize the connection between fracture risk and bone active medication.

Prior fragility fractures are associated with a higher risk of 8-year complications following total shoulder arthroplasty.

As the population ages, more patients with osteoporosis are undergoing total shoulder arthroplasty (TSA), including those who have sustained a prior fragility fracture. Sustaining a fragility fracture before TSA has been associated with increased risk of short-term revision rates, periprosthetic fracture (PPF), and secondary fragility fractures but long-term implant survivorship in this patient population is unknown. Therefore, the purpose of this study was to characterize the association of prior fragility fractures with 8-year risks of revision TSA, periprosthetic fracture, and secondary fragility fracture. Patients aged 50years and older who underwent TSA were identified in a large national database. Patients were stratified based on whether they sustained a fragility fracture within 3years prior to TSA. Patients who had a prior fragility fracture (7631) were matched 1:1 to patients who did not based on age, gender, Charlson Comorbidity Index (CCI), smoking, obesity, diabetes mellitus, and alcohol use. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences of all-cause revision, periprosthetic fracture, and secondary fragility fracture within 8years of index surgery. The 8-year cumulative incidence of revision TSA (5.7% vs. 4.1%), periprosthetic fracture (3.8% vs. 1.4%), and secondary fragility fracture (46.5% vs. 10.1%) were significantly higher for those who had a prior fragility fracture when compared to those who did not. On multivariable analysis, a prior fragility fracture was associated with higher risks of revision (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.24-1.74; p < 0.001), periprosthetic fracture (HR, 2.98; 95% CI, 2.18-4.07; p < 0.001) and secondary fragility fracture (HR, 8.39; 95% CI, 7.62-9.24; p < 0.001). Prior fragility fracture was a significant risk factor for revision, periprosthetic fracture, and secondary fragility fracture within 8years of primary TSA. Identification of these high-risk patients with an emphasis on preoperative and postoperative bone health optimization may help minimize these complications. III.

Association of fluoride exposure with disease burden and neurodevelopment outcomes in children in South Korea.

Community water fluoridation is an effective public health strategy for preventing dental caries, yet. Concerns exist about potential health problems. This study explores associations between tap water fluoride levels and pediatric disease burden, as well as neurodevelopmental outcomes at 6years of age. This nationwide population-based cohort study included children born in Korean cities with and without tap water fluoridation projects, between 2006 and 2012, aiming for a fluoride concentration of 0.8 ± 0.2mg/L in treated tap water. Data from the National Health Insurance Service were used, spanning from birth to 2018. The relationship between exposure to fluoridated tap water and incidence of 16 childhood diseases that were previously identified as potentially linked to fluoride exposure were examined. Additionally, we evaluated the neurodevelopmental outcomes across various domains, including gross motor, fine motor, cognition, language, social skills, and self-help functions. These assessments were performed using data from a comprehensive national health screening program for children aged six years. A fluoride-unexposed group included 22,881 children, whereas a fluoride-exposed group comprised 29,991 children (52% males). Children in the fluoride-exposed group had a decreased risk of dental caries and bone fractures [hazard ratio (95% confidence interval, CI), 0.76 (0.63-0.93) and 0.89 (0.82-0.93), respectively] and increased risk of hepatic failures [1.85, (1.14-2.98)] compared to those in the unexposed group. Additionally, the risk ratio of abnormal neurodevelopmental screening outcomes increased by 9%, but this was statistically uncertain (95% CI, 0.95-1.26). Fluoridated tap water was associated with an increased risk of hepatic failure but a decreased risk of bone fractures in children. The association between fluoridated tap water and neurodevelopmental screening outcomes at 6years remains unclear, highlighting the need for further studies to clarify this association.

Total Hip Arthroplasty in Hip Osteoarthritis with Subtrochanteric Localized Periosteal Thickening: Preoperative Planning Using Finite Element Analysis to Determine the Optimal Stem Length

Background: Owing to the risk of atypical femoral fractures, total hip arthroplasty presents unique challenges for patients with ipsilateral osteoarthritis and localized periosteal thickening in the femoral subtrochanteric region. Stem length selection is critical for minimizing stress concentration in the thickened cortex to avoid such fractures. Herein, we report the case of a 78-year-old woman with ipsilateral hip osteoarthritis and localized subtrochanteric periosteal thickening. Methods: Preoperative planning included a finite element analysis to assess the stress distribution across various stem lengths. A simulation was conducted to determine the optimal stem length to span the cortical thickening and reduce the risk of postoperative complications. Results: The finite element analysis indicated that a stem length of &gt;150 mm was required to effectively reduce the stress at the site of cortical thickening. A 175 mm stem was selected for total hip arthroplasty, which provided a favorable stress distribution and avoided the risk of stress concentration. Conclusions: In cases of ipsilateral osteoarthritis with localized subtrochanteric periosteal thickening, finite element analysis can be valuable for preoperative planning to determine the optimal stem length, thereby reducing the risk of atypical femoral fractures. Further studies with multiple cases are recommended to validate these findings and improve surgical outcomes.

Osteoporosis and inflammation: Cause to effect or comorbidity?

Osteoporosis (OP) was long viewed as an inevitable process of aging, due to an imbalance between osteoclast bone resorbing and osteoblast bone formation function, leading to a negative balance in bone remodeling. This leads to low bone mass and increased bone fragility putting the patient at risk for fracture. While this view still holds, a better understanding disclosed that OP can occur at any age, as a comorbidity or a complication of many diseases and treatments. Differentiation, maturation, and function of osteoclasts and osteoblasts are affected by many factors from different morbidities: endocrine, metabolic, mechanical and inflammatory. Inflammatory diseases are often complicated by a generalized bone loss that subsequently leads to OP. Factors such as glucocorticoid treatment, immobilization, malnutrition, and insufficient intake of vitamin D play a role. However, the inflammatory process itself is involved and the resulting bone loss is termed immune-mediated bone loss. Experiments on animals and on humans, in addition to clinical studies, shed light on the role of inflammation in OP.

Predictors of lumbar spine trabecular bone score in women with postsurgical hypoparathyroidism

Hypoparathyroidism is a rare disease that markedly reduces bone remodeling, leading to increased bone mineral density and changes in bone microarchitecture. However, it is currently unclear how these changes affect fracture risk. In this study, we investigated bone mass by dual-energy x-ray absorptiometry, the occurrence of morphometric vertebral fractures, and bone microarchitecture by assessing trabecular bone score in women with postsurgical hypoparathyroidism. We included 67 women with hypoparathyroidism aged 52.9 ± 12.3 years and 63 age (52.9 ± 12.3 years) and body mass index-matched controls, which were assessed for femoral and lumbar spine bone mineral density, trabecular bone score, and vertebral fractures by dual-energy x-ray absorptiometry. Women with hypoparathyroidism had significantly higher bone mineral density at the lumbar spine, femoral neck, and total hip compared with controls despite similar trabecular bone score values. Vertebral fracture assessment indicated that two women with hypothyroidism presented vertebral fractures, both aged over 65 years. Conversely, no vertebral fractures were detected in control women. In a multivariate linear regression model, we found that older age, diabetes, and lower lumbar spine mineral density were significant predictors of lower trabecular bone score values. Our findings indicate that vertebral fractures are not common among women with postsurgical hypoparathyroidism aged under 65 years. Moreover, trabecular bone score values were similar in women with hypoparathyroidism and age-matched controls and were associated with traditional risk factors for fractures, such as older age, type 2 diabetes, and lower spine bone mineral density. Lay summaryChronic parathyroid hormone deficiency decreases bone turnover and modifies skeletal properties, although the impact of these changes on fracture risk remains unclear. We studied 67 women with postsurgical hypoparathyroidism and 63 age and body mass index-matched healthy controls and found that bone mineral density is increased in women with hypoparathyroidism despite similar trabecular bone score values and a low occurrence of morphometric vertebral fractures. This suggests that the low bone turnover in hypoparathyroidism increases bone mass, but this is not accompanied by improved bone microarchitecture, indicating that trabecular bone score may be a valuable tool to complement the assessment of skeletal health and the risk of fractures in this condition.

Trabecular Bone Score to Enhance Fracture Risk Prediction and Treatment Strategies in Osteoporosis.

The Trabecular Bone Score (TBS), a gray-level textural assessment derived from dual-energy X-ray absorptiometry images, serves as a validated index of trabecular bone microarchitecture. Over the past decade, significant evidence has highlighted the usefulness of TBS in primary and secondary osteoporosis, leading to its integration with the Fracture Risk Assessment Tool (FRAX) and bone mineral density (BMD) T-score adjustments. This review explores the role of TBS in fracture prediction, treatment initiation, and monitoring. Studies confirm that TBS enhances fracture risk prediction in both primary and secondary osteoporosis when combined with BMD and clinical risk factors. Evidence also suggests that including TBS alongside BMD and FRAX offers significant potential for treatment stratification, considering the overall skeletal profile, such as bone mass, bone quality, and clinical risk factors. Consequently, TBS has become a standard part of clinical care worldwide. Future enhancements hope to adjust for soft tissue thickness, broadening the applicability of TBS across diverse body types and pediatric populations.

Bone Phenotype and Fracture Risk in Patients with Type 2 Diabetes at the Time of Kidney Transplantation

Bone Phenotype and Fracture Risk in Patients with Type 2 Diabetes at the Time of Kidney Transplantation

Multidisciplinary Team Evaluation of Bone Health, Fracture Risk, and Incidence of Frailty in Patients on Haemodialysis

Multidisciplinary Team Evaluation of Bone Health, Fracture Risk, and Incidence of Frailty in Patients on Haemodialysis

Research

The October 2024 Research Roundup360 looks at: Fracture risk among stroke survivors according to post-stroke disability status and stroke type; Noise-induced hearing loss: should surgeons be wearing ear protection during primary total joint replacement?; Intravenous dexamethasone in hip arthroscopy can enhance recovery; Patient-reported outcomes following periprosthetic joint infection of the hip and knee: a longitudinal, prospective observational study; When should surgery take place after weight loss?; Which type of surgery is the hardest physically and mentally?

SGLT2 Inhibitors and Fracture Risk in Individuals with Advanced CKD

SGLT2 Inhibitors and Fracture Risk in Individuals with Advanced CKD