Impaired Bone Health Research Articles

Relative Energy Deficiency in Sport: an Orthopaedic Perspective.

Relative energy deficiency in sport (RED-S) is a constellation of clinical findings related to low energy availability. Manifestations are variable but may include endocrine and reproductive dysfunction, impaired bone and muscle health, psychological complaints, and performance issues, among many others. Unlike the previously common terminology, the female athlete triad, RED-S encompasses a broader range of signs and symptoms and includes descriptions for the male athlete. Since first being described in 2014 by the International Olympic Committee, an abundance of research has sought to define, prevent, and treat the underlying condition of RED-S. Although medicine, and society in general, has tried to expose the hazardous training and lifestyle behaviors that can underpin RED-S, further research and education is required on the part of the clinician and athlete to reshape the culture and prevent the deleterious consequences of low energy availability.

Association between developmental coordination disorder or low motor competence, and risk of impaired bone health across the lifespan: protocol for a systematic review and meta-analysis.

This systematic review will assess the association between developmental coordination disorder or low motor competence and impairments in bone health across the lifespan. Individuals with developmental coordination disorder tend to have a pattern of physical activity associated with bone health impairments. Preliminary studies have found impairments in bone health measures, including fractures, throughout the lifespan with potential public health ramifications. As studies in this area are of small samples across wide age ranges, no comprehensive picture of bone health in this group has been formed, hindering action. A systematic review is needed to determine the potential risk of bone impairment in this population. Studies that assess the relationship between developmental coordination disorder/low motor competence and bone health, regardless of measures used, will be included in the review. There will be no exclusions based on region, study design, or participant demographic characteristics. Published studies and gray literature will be searched, with no limits on publication date or language. Assessment of studies for inclusion, as well as data extraction, will be performed by two reviewers, with data cross checked for accuracy. Studies will be appraised using the appropriate JBI tool for the study design. Data to be extracted include unadjusted results and effect sizes for bone health measures. A narrative synthesis will be performed and if there is a sufficient number of studies, a meta-analysis using the same outcome measures will be performed on odds ratios of abnormal bone phenotype and fracture in this population. PROSPERO CRD42020167301.

Gestational perfluoroalkyl substance exposures and early adolescent bone mineral density in the HOME Study

Background/Aim: Perfluoroalkyl substances (PFAS) may impair bone health via endocrine disruption and nuclear hormone receptor activation. Bone mineral accrual during adolescence is important for long-term bone health, but human studies of PFAS and bone mineral density are primarily in adults or use a cross-sectional study design. We estimated associations of gestational PFAS exposures with early adolescent areal bone mineral density (aBMD) in a prospective cohort study. Methods: We examined 225 pregnant mothers enrolled from 2003-2006 in Cincinnati, OH and their children in the HOME Study. We measured concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononaoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) in maternal serum collected at 16 weeks gestation. When children were 12 years old, we measured lean body mass and total body, spine, total hip, femoral neck, and distal forearm (1/3 radius) aBMD with dual x-ray absorptiometry and calculated height-, age-, sex-, and race-specific aBMD z-scores. Using linear regression, we estimated covariate-adjusted associations in aBMD z-scores per doubling of gestational PFAS concentrations overall and stratified by sex. We estimated the proportion of total effects that were mediated by lean mass using structural equation modeling. Results: In adjusted models, higher PFOA concentrations were associated with lower aBMD z-scores of the forearm (β: -0.28, 95% CI: -0.49, -0.08), total hip (β: -0.28, 95% CI: -0.54, -0.02), and spine (β: -0.34, 95% CI: -0.61, -0.06) in males but not females. Lean mass mediated 29-50% of these associations. Higher PFHxS and PFNA concentrations were associated with lower aBMD z-scores of the forearm (PFHxS β: -0.11, 95% CI: -0.23, 0.00; PFNA β: -0.14, 95% CI: -0.35, 0.06), with no modification by sex or mediation by lean mass. PFOS was not associated with aBMD measures in either sex. Conclusions: Gestational PFAS exposures may reduce bone accrual in early adolescence, possibly in a sex-dependent manner.

Bone health in young adult survivors born extremely preterm or extremely low birthweight in the post surfactant era.

Most infants born extremely preterm (EP; <28weeks' gestation) or extremely low birthweight (ELBW; <1000g birthweight) in the post surfactant era (early 1990s) are now surviving into adulthood. Preterm birth/low birthweight are risk factors for reduced bone growth and mineralisation in infants and children. However, little is known about their bone health around peak bone mass and through adult life. To compare bone health (bone mineral measures, bone structure and strength) in young adults born EP/ELBW with controls (>2499g birthweight), and within the EP/ELBW group examine perinatal and later variables associated with long term bone health. A geographic cohort comprising all 297 survivors born EP/ELBW in 1991-92 in the state of Victoria, Australia, and 260 contemporaneous controls (>2499g birthweight) were recruited into a longitudinal study from birth. At age 25years, investigations included dual energy X ray absorptiometry and peripheral quantitative computed tomography to measure bone, muscle and soft tissue variables, and fasting blood samples to measure serum 25 hydroxyvitamin D (25(OH)D) and bone turnover markers (BTM). Linear regression analysis, with models fitted using generalised estimating equations, was used to compare outcomes between groups, adjusting for height and weight. Compared with controls (n=129), young adults born EP/ELBW (n=162) had lower areal bone mineral density (g/cm2) (mean difference [MD] -0.044; 95% confidence interval [CI] -0.076,-0.013) and Z-scores (MD -0.53; 95% CI -0.75, -0.30) in the femoral neck, and lower total hip Z-score (MD -0.35; 95% CI -0.54, -0.15) after adjusting for height and weight. EP/ELBW males generally displayed more bone and soft tissue deficits than females, compared with their respective controls. Within the EP/ELBW group, early growth, male sex, height and lean mass, muscle measures, 25(OH)D levels, and BTM were independently associated with bone mineral measures, structure or strength. Young adults born EP/ELBW had evidence of impaired bone health around the age of peak bone mass compared with controls. Further follow-up of the EP/ELBW groups will determine if they have a heightened low-trauma fracture risk in later life.

Body Composition and Bone Mineral Density in Craniopharyngioma Patients: A Longitudinal Study Over 10 Years.

Patients with craniopharyngioma suffer from obesity and impaired bone health. Little is known about longitudinal changes in body composition and bone mineral density (BMD). To describe body composition and BMD (change). Retrospective longitudinal study. Two Dutch/Swedish referral centers. Patients with craniopharyngioma (n = 112) with a dual X-ray absorptiometry (DXA) scan available (2 DXA scans, n = 86; median Δtime 10.0 years; range 0.4-23.3) at age ≥ 18 years (58 [52%] male, 50 [45%] childhood onset). Longitudinal changes of body composition and BMD, and associated factors of ΔZ-score (sex and age standardized). BMI (from 28.8 ± 4.9 to 31.2 ± 5.1 kg/m2, P < .001), fat mass index (FMI) (from 10.5 ± 3.6 to 11.9 ± 3.8 kg/m2, P = .001), and fat free mass index (FFMI) (from 18.3 ± 3.2 to 19.1 ± 3.2 kg/m2, P < .001) were high at baseline and increased. Fat percentage and Z-scores of body composition did not increase, except for FFMI Z-scores (from 0.26 ± 1.62 to 1.06 ± 2.22, P < .001). Z-scores of total body, L2-L4, femur neck increased (mean difference 0.61 ± 1.12, P < .001; 0.74 ± 1.73, P < .001; 0.51 ± 1.85, P = .02). Linear regression models for ΔZ-score were positively associated with growth hormone replacement therapy (GHRT) (femur neck: beta 1.45 [95% CI 0.51-2.39]); and negatively with radiotherapy (femur neck: beta -0.79 [-1.49 to -0.09]), glucocorticoid dose (total body: beta -0.06 [-0.09 to -0.02]), and medication to improve BMD (L2-L4: beta -1.06 [-1.84 to -0.28]). Z-scores of BMI, fat percentage, and FMI remained stable in patients with craniopharyngioma over time, while Z-scores of FFMI and BMD increased. Higher glucocorticoid dose and radiotherapy were associated with BMD loss and GHRT with increase.

Prevalence of Osteopathologies in Children and Adolescents After Diagnosis of Acute Lymphoblastic Leukemia.

Background: Impaired bone health is a late effect of childhood malignancies which can be difficult to detect in juvenile survivors. It may, however, lead to compromised quality of life, or even permanent disability later in life due to osteoporosis, pain or fractures if left untreated. Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy with an over 85% five-year survival. ALL and its treatment cause bone alterations in adults, but little information on the bone health status in juvenile survivors is available.Objective: To report data on skeletal late effects in juvenile survivors of childhood ALL based on a comprehensive assessment of bone health and to assess the influence of a vitamin D deficiency on bone health in this cohort.Methods: In a single center cross sectional study 128 pediatric patients (11.9 ± 4.76 years) with a mean follow up of 5.88 ± 3.75 years after diagnosis of ALL were recruited. The bone health status of the survivors was assessed based on clinical examination, review of medical records, biochemical and radiographic analyses, by clinical experts. A score which utilized 8 different parameters was formed and used to assess the effect of a vitamin D deficiency on bone health.Results: In this cohort, 18% of survivors displayed overt osteopathologies as defined by clinical expert assessment. Impaired bone health, defined by at least one pathological screening parameter, was detected in 77%. Despite recommendations for adequate vitamin D supplementation, 15% displayed a vitamin D deficiency associated with hyperparathyroidism. The applied score identified survivors with osteopathologies with high sensitivity and specificity. The median score did not differ between patients without and with severe vitamin D deficiency.Conclusion: Our findings suggest that impaired bone health and osteopathologies are common skeletal late effects following treatment of childhood ALL. Major contributing factors are BMT, irradiation and older age at diagnosis. Vitamin D deficiency likely accounts for hyperparathyroidism in some patients but does not seem to further affect bone health in this cohort. Survivors of ALL need thorough surveillance to investigate bone health, since bone morbidity is common and still poorly understood. Early detection and appropriate intervention may improve bone health.

Impaired bone health at cancer diagnosis in paediatric patients

Impaired bone health at cancer diagnosis in paediatric patients

Impaired Bone Health in Children With Biliary Atresia.

The aim of the study was to examine the frequency of rickets and bone fractures and to assess areal bone mineral density (aBMD) in childhood among patients with biliary atresia (BA). We gathered data on all patients diagnosed with BA in Finland that survived to ≥1 year of age between 1 January 2000 to 30 June 2018. Data on gestational age, birth weight, postsurgical medications, and history of rickets and bone fractures were collected retrospectively. Serum levels of 25-hydroxyvitamin D [25(OH)D] postportoenterostomy (PE) were collected. Plain radiographs and dual energy X-ray absorptiometry (DXA) measurements of study subjects were reviewed. Out of 49 patients, 7 (14%) were diagnosed with rickets during infancy. Clearance of jaundice [odds ratio 0.055, 95% confidence interval [CI] 0.00266-0.393; P < 0.01] was a protective factor against rickets. Sufficient 25(OH)D levels were reached 3 months post-PE. Eleven (22%) patients suffered at least one bone fracture (range 1-9) during childhood and adolescence. In DXA measurements, median lumbar spine aBMD anthropometrically adjusted z-scores were as follows: in native liver survivors 0.8 (interquartile range [IQR] -1.9 to 1.4) at 5 and -0.3 (IQR -1.3 to 0.8) at 10 years and for liver transplanted patients 0.4 (IQR -0.2 to 1.1) at 5 and 0.6 (IQR -0.1 to 1.3) at 10 years. BA patients have an increased risk for rickets and bone fractures compared with the normal population. Most BA patients have aBMD within normal range between 5 and 10 years of age irrespective of liver transplantation status.

Proanthocyanidin-rich grape seed extract improves bone loss, bone healing, and implant osseointegration in ovariectomized animals

The purpose of the present study was to confirm if proanthocyanidin-rich grape seed extract (GSE) had the ability to improve bone health such as bone loss, bone healing, and implant osseointegration (defined as the direct connection between bone tissue and an implant) in ovariectomized (OVX) animals. We demonstrated that daily oral administration of GSE prevented bone loss in the lumbar vertebrae and femur in OVX mice. In addition, osteoclastogenesis in the lumbar spine bone of OVX mice, as assessed by histological and histomorphometric analyses, was accelerated but GSE prevented this dynamization, suggesting that GSE could counteract OVX-induced accelerated osteoclastogenic activity. In rats, OVX clearly impaired the healing of defects created on the calvaria, and GSE overcame this OVX-impaired healing. In the same way, osseointegration of a tibial implant in rats was retarded by OVX, and GSE counteracted the OVX-induced poor osseointegration, likely promoting bone healing by preventing imbalanced bone turnover. These results suggest that orally administered GSE improved implant osseointegration by mitigating the impaired bone health induced by OVX as a model of estrogen deficiency.

Selective serotonin reuptake inhibitors (SSRI) affect murine bone lineage cells

AimsData suggest pharmacological treatment of depression with selective serotonin reuptake inhibitors (SSRI) may impair bone health. Our group has previously modeled compromised craniofacial healing after treatment with sertraline, a commonly prescribed SSRI, and hypothesized potential culprits: alterations in bone cells, collagen, and/or inflammation. Here we interrogate bone lineage cell alterations due to sertraline treatment as a potential cause of the noted compromised bone healing. Main methodsMurine pre-osteoblast, pre-osteoclast, osteoblast, and osteoclast cells were treated with clinically relevant concentrations of the SSRI. Studies focused on serotonin pathway targets, cell viability, apoptosis, differentiation, and the osteoblast/osteoclast feedback loop. Key findingsAll cells studied express neurotransmitters (e.g. serotonin transporter, SLC6A4, SSRI target) and G-protein-coupled receptors associated with the serotonin pathway. Osteoclasts presented the greatest native expression of Slc6a4 with all cell types exhibiting decreases in Slc6a4 expression after SSRI treatment. Pre-osteoclasts exhibited alteration to their differentiation pathway after treatment. Pre-osteoblasts and osteoclasts showed reduced apoptosis after treatment but showed no significant differences in functional assays. RANKL:OPG mRNA and protein ratios were decreased in the osteoblast lineage. Osteoclast lineage cells treated with sertraline demonstrated diminished TRAP positive cells when pre-exposed to sertraline prior to RANKL-induced differentiation. SignificanceThese data suggest osteoclasts are a likely target of bone homeostasis disruption due to sertraline treatment, most potently through the osteoblast/clast feedback loop.

SUN-382 Craniopharyngioma Patients Are at Risk of Impaired Bone Health

IntroductionCraniopharyngioma (CP) are benign tumors originating from the sellar/hypothalamic region that are associated with neurological damage, epilepsy and endocrinopathies, which all could negatively affect bone health. Our objective was to determine fracture risk, bone mineral density (BMD) and final height in CP and evaluate independent determinants for fractures.MethodsIn this retrospective study, Dutch/Swedish patients with CP were included if data was available on fractures, bone mineral density (BMD) (T/Z-score), or final height (age >18 years). Data is presented as mean±SD unless stated otherwise. Logistic regression models were developed to evaluate determinants for fractures and osteoporosis. Low BMD was defined as T- or Z-score ≤-1 and osteoporosis as ≤-2.5 or ≤-2.0, respectively.ResultsWe included 177 patients (48% female, 48% childhood-onset disease), with a median age at last follow-up of 45 years (range 15-92 years). Fractures occurred in 31 patients (18%); a fracture rate of 5.8 per 1000 person years. Eight patients suffered from multiple fractures (26%). In a multivariable logistic regression model for fractures, significant protective factors were female sex (OR 0.3 P=0.004) and surgery (OR 0.1, P=0.009), whereas a risk factor was use of anti-epileptics (OR 3.0, P=0.07). A significant risk factor for osteoporosis was age (OR 1.03, P=0.03); growth hormone replacement therapy tended to be protective (OR 0.2, P=0.10). Osteoporosis was not an explanatory variable for fractures (OR 2.1, P=0.21). Mean BMD T- and Z-scores were normal: Z-scores for L2-L4, femur neck and total body were 0.0±2.0 (range -3.5 - 6.8), -0.1±1.3 (range -2.7 - 4.7) and 0.1±1.5 (range -4.1 - 3.5), respectively. Osteoporosis occurred in 22 patients (24%); mean age of patients with osteoporosis was 53 ± 20 years. Low BMD occurred in 47 patients (50%). Medication to improve BMD was less often used in men than in women(7% vs. 18%, P=0.02). Mean final height was normal and did not differ between males/females, or adulthood/childhood-onset patients.ConclusionsPatients with CP have a high fracture rate. In this population, epilepsy treatment was a risk factor, female sex a protective factor whereas osteoporosis did not affect the risk for fractures. Mean BMD Z-score was normal, but with a very wide range, resulting in low BMD in 50% and osteoporosis in 24% of the patients. Male CP patients are potentially undertreated with medication to improve bone health.

High serum FSH is not a risk factor for low bone mineral density in infertile men.

Male infertility is associated with a higher long-term morbidity and mortality risk. However, it is not clear which diseases are contributing to this risk. Osteoporosis is a possible factor, as it is a frequent disease and sex steroids regulate both fertility and bone health. Furthermore, there are data indicating that high FSH levels in women are related to low bone mineral density (BMD), independent of estradiol levels. As infertile men often have increased FSH, already from a young age, this could be a risk factor for impaired bone health in later life. One hundred and thirty-seven men with a history of male factor infertility due to spermatogenic failure (SgF men) as well as a control group of 70 men from couples treated with IVF for female factor infertility (non-SgF men) were included in a long-term follow-up study. Men with explained infertility, including testosterone deficiency, were not included. Data from baseline fertility investigations were retrieved from the patient files of the SgF men. At follow-up hormonal and semen analysis were performed and axial, femoral and total body BMD was measured by dual X-ray absorptiometry in all men. Multiple linear regression was used to assess differences between SgF and non-SgF men and to study associations between FSH levels and BMD. Median follow-up time was 14.8years (5th-95th percentile 11.3-18.2) after fertility assessment for SgF men and 15.6years (12.1-18.5) for non-SgF men (p=0.033). When comparing the two groups, no significant differences in total T, free T or E2 levels were apparent at follow-up. As expected, LH and FSH were higher in SgF men ((median (5th-95th percentile)) for LH (IU/L): 4.3 (2.2-13.6) for SgF men and 3.0 (1.4-5.8) for non-SgF men (p<0.001); FSH (IU/L): 9.8 (2.8-35.5) versus 3.7 (1.6-8.7); p<0.001), and inhibin B and semen parameters were lower in SgF men. There were no differences in BMD between the two groups at follow-up. Furthermore, both groups had median Z-scores close to zero at all sites, indicating that BMD is not different when compared to age-matched healthy men. In SgF men, neither baseline FSH, nor FSH at follow-up, was associated with BMD at the different sites at follow-up. Men with spermatogenic failure are not at increased risk for impaired bone health when middle aged. Furthermore, infertile men with high FSH levels do not have lower BMD.

Decreased markers of bone turnover in children and adolescents with type 1 diabetes.

Adults with type 1 diabetes (T1D) have increased risk of bone fractures and decreased bone mineral density (BMD). Alterations in bone turnover have been suggested as the link between T1D and the impaired bone health. Furthermore, bone turnover has been suggested to have beneficial effects on glucose metabolism. This study aimed at describing bone turnover markers (BTM), and the relationship with glycemic control, in children and adolescents with T1D. A total of 173 (47% girls) children and adolescents aged 7.7 to 17.5 years with T1D for more than 1 year were included. Participants were evaluated by BMD together with measurements of selected BTM; two formation markers: osteocalcin (OCN) and procollagen type-1 amino-terminal propeptide (P1NP) and one resorption marker, C-terminal cross-linked telopeptide of type-1 collagen (CTX). BTM were converted into Z-scores utilizing new national references. Mean OCN Z-score (-0.68 ± 1.31), P1NP Z-score (-0.33 ± 1.03) and CTX Z-score (-0.43 ± 1.10) were all significantly lower than the reference population (P < .001). No associations were seen between BTM and T1D duration. BMD Z-score was comparable to the reference population and associated with none of individual BTMs. CTX Z-score was negatively associated with HbA1c (P = .007) independent of both exogenous and residual endogenous insulin. Markers of bone formation and resorption were decreased in children and adolescents with T1D. CTX Z-score associated negatively with HbA1c adjusted for insulin treatment and endogenous insulin production indicating a potential association between CTX and insulin sensitivity. The long-term consequences of decreased BTM on BMD need further attention.

Low bone mineral density is associated with hypogonadism and cranial irradiation in male childhood cancer survivors

SummaryWe investigated if bone mineral density was related to testosterone deficiency and/or previous cancer treatment in men who were childhood cancer survivors. Men with untreated testosterone deficiency or previous treatment with cranial irradiation were at increased risk of impaired bone health. Prevention of osteoporosis should be considered in their follow-up.IntroductionChildhood cancer survivors (CCS) are at increased risk of hypogonadism. Reduced bone mineral density (BMD) has been reported in CCS but it is unclear whether this is due to hypogonadism or a direct effect of cancer therapy. This study investigated BMD in CCS, and association with hypogonadism, previous treatment and cancer type.MethodsInvestigation of 125 CCS (median age 33.7 at inclusion; 9.6 at diagnosis) and 125 age-matched population controls. Serum testosterone and luteinizing hormone were assayed and BMD at total hip and lumbar spine L1–L4 measured. The mean difference in BMD (g/cm2; 95% CI) between CCS and controls was analysed. Odds ratios (OR; 95% CI) for low BMD were also calculated.ResultsOverall, BMD in the CCS cohort did not significantly differ from controls. However, compared with eugonadal CCS, the CCS with untreated hypogonadism had lower BMD at the hip (mean difference − 0.139 (− 0.210; − 0.067); p < 0.001) and spine (− 0.102 (− 0.174; − 0.030); p = 0.006). They also had a higher risk of low hip BMD (OR 4.1 (1.3; 14); p = 0.018). CCS treated with cranial irradiation also had lower BMD (hip − 0.076 (− 0.133; − 0.019); p = 0.009; spine − 0.071 (− 0.124; − 0.018); p = 0.009) compared with controls. The latter associations remained statistically significant after adjustment for hypogonadism.ConclusionsCCS with hypogonadism or previously treated with cranial irradiation are at increased risk of impaired bone health. Prevention of osteoporosis should be considered as an important part in future follow-up of these men.

Bone Turnover Markers and Probable Advanced Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Men and Postmenopausal Women With Type 2 Diabetes

Objective: Type 2 diabetic patients have a higher incidence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis, and nonalcoholic fatty liver disease (NAFLD) is associated with impaired bone health. We aimed to investigate whether bone turnover is associated with the probable presence of NASH and fibrosis.Methods: In total, 4,937 diabetic participants from Shanghai, China were enrolled in 2018. Subjects with NAFLD were categorized into simple NAFLD and probable NASH groups based on the presence of a metabolic syndrome. The NAFLD fibrosis score was used to identify patients with a higher likelihood of advanced fibrosis.Results: In postmenopausal women, large N-mid fragment of osteocalcin (N-MID osteocalcin) was negatively associated with probable NASH (P for trend < 0.001). β-C-terminal cross-linked telopeptides of type I collagen (β-CTX) and procollagen type I N-terminal propeptide (P1NP) were positively associated with the probable presence of significant fibrosis in postmenopausal women (P for trend 0.015 and <0.001). However, in men, N-MID osteocalcin and β-CTX were negatively associated with the probable presence of significant fibrosis (P for trend 0.029 and 0.027).Conclusions: Significant associations among N-MID osteocalcin, β-CTX and P1NP, and probable advanced NAFLD were observed. Further prospective and animal studies are warranted to understand the causal relationship and underlying mechanism.

Bone Health Optimization in Orthopaedic Surgery.

Osteoporosis is associated with adverse orthopaedic surgical outcomes. Bone health optimization is a preoperative intervention intended to reduce the likelihood of postoperative complications. We aimed to characterize a patient cohort referred for bone health optimization to test the hypothesis that poor bone quality is common in orthopaedic surgery and that many such patients meet guidelines for osteoporosis treatment. This retrospective study evaluated 124 patients referred for bone health optimization who were ≥50 years of age and candidates for arthroplasty or thoracolumbar surgery. The Fracture Risk Assessment Tool (FRAX) risk factors and dual x-ray absorptiometry (DXA) results were collected. When available, opportunistic computed tomographic (CT) imaging and the trabecular bone score were evaluated. The World Health Organization (WHO) diagnostic and National Osteoporosis Foundation (NOF) treatment guidelines were applied. All patients were referred by their orthopaedic surgeon; their mean age was 69.2 years, 83% of patients were female, 97% were Caucasian, and 56% had sustained a previous fracture. The mean historical height loss (and standard deviation) was 5.3 ± 3.3 cm for women and 6.0 ± 3.6 cm for men. The mean lowest T-score of the hip, spine, or wrist was -2.43 ± 0.90 points in women and -2.04 ± 0.81 points in men (p < 0.08). Osteoporosis (T-score of ≤-2.5 points) was present in 45% of women and 20% of men; only 3% of women and 10% of men had normal bone mineral density. Opportunistic CT scans identified 60% of patients as likely having osteoporosis. The trabecular bone score identified 34% of patients with degraded bone microarchitecture and 30% of patients with partially degraded bone microarchitecture. The NOF threshold for osteoporosis treatment was met in 91% of patients. Treatment was prescribed in 75% of patients (45% anabolic therapy and 30% antiresorptive therapy). Osteoporosis, degraded bone microarchitecture, prior fracture, and elevated fracture risk were common. Given the high prevalence of impaired bone health in this cohort, we believe that bone health screening, including FRAX assessment, should be considered in selected patients undergoing orthopaedic surgery as part of the preoperative optimization for all adults who are ≥50 years of age. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Bone Health in Glomerular Kidney Disease.

To summarize the literature regarding alterations in bone health in patients with glomerular kidney disease and highlight areas in need of additional investigation. There is mounting evidence that children and adults with glomerular conditions, with or without compromised kidney function, comprise a distinct subgroup of patients with unique risk factors for altered bone health. Patients with glomerular kidney disease are exposed to both disease-related and treatment-related factors that affect bone structure and function. In addition to chronic kidney disease-related risk factors for impaired bone health, high rates of exposure to osteotoxic medications, varying degrees of systemic inflammation, and altered vitamin D metabolism may contribute to compromised bone health in individuals with glomerular disease. Further study is needed to better understand these risk factors and the complex interaction between the immune system and bone cells in glomerular disease.

Impaired Bone Health and Wound Dehiscence in Carriers of Hemophilia a and B

Introduction: FVIII and FIX have a well-established pivotal role in the promotion and maintenance of hemostasis. There is emerging evidence, however, for a role of FVIII and FIX in regulating processes beyond thrombin generation, such as bone health and macrophage function affecting wound healing. Previous studies on bone mineral density (BMD) and fractures have primarily investigated persons with hemophilia A (PwHA) and hemophilia B (PwHB), but not hemophilia carriers. It has been estimated that 35% of hemophilia carriers have FVIII and FIX levels below 40IU/dL. However, it is not known if hemophilia carriers have a similar potential to develop decreased BMD and poor wound healing as PwHA or PwHB. This study aims to assess the prevalence of bone health issues and wound healing among women who are hemophilia carriers comparing them to control women in the general population. Methods: A commercial database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems, was queried for data, using Systematized Nomenclature of Medicine (SNOMED) clinical terms or codes. Cases were defined as female patients of any age, with a diagnosis of Hemophilia carrier. Controls were defined as female patients of any age, with at least one medical encounter, and who did not have a diagnosis of Hemophilia Carrier. The prevalence rates of osteoporosis, osteoarthritis, fractures and wound dehiscence among cases and controls were estimated based on binomial distribution theory. The prevalence rates of the comorbidities were compared in the Hemophilia Carrier group and control group using chi-square or Fisher's exact test, and relative risk calculations for bone health issues were adjusted for age &amp;gt; 50, as the risk of osteoporosis and osteoporotic fractures is higher in post-menopausal women above the age of 50. Results: Our database search identified 740 hemophilia carriers and 34,129,790 women in the control group (Table 1). Among the hemophilia carrier group, there was increased prevalence of osteoporosis (7% vs 3.6%, p&amp;lt;0.0001), osteoarthritis (26% vs 11%, p&amp;lt;0.0001), and fractures (12% vs 6%), p&amp;lt;0.0001) as compared to the control group. Wound dehiscence had a prevalence of 270 cases per 10,000 in the hemophilia carrier group, vs 120 per 10,000 in the control group. The age-adjusted relative risk of osteoporosis, osteoarthritis, and fractures due to hemophilia was 2.72 (95% CI 2.20 to 3.41), 2.85 (95% CI: 2.55 to 3.17), and 2.57 (95% CI: 2.16 to 3.05), respectively (Table 2). Conclusions: Our study suggests an association between hemophilia carrier state and poor bone health and wound healing. Prospective studies are required to confirm these findings, including the role of factor levels in these patients in relation to bone turnover markers and macrophage function. This data may also have relevance for the importance of exposure to factor in the era of emerging non-factor therapies in hemophilia. Disclosures Ahuja: Genentech: Consultancy; Biovertiv Sanofi: Consultancy; Bayer: Consultancy; Rainbow Children's Foundation: Research Funding; XaTexk Inc.: Consultancy, Patents &amp; Royalties, Research Funding.

Cardiometabolic risk, body composition and bone health in children and adolescents in long-term remission of acute lymphoblastic leukemia - a study protocol

Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of cardiometabolic abnormalities, altered body composition (obesity and sarcopenia) and impaired bone health. These adverse sequelae progress through childhood and adulthood, worsening survivors` quality of life and resulting in cardiovascular conditions, metabolic syndrome (MetS), osteoporosis and related disabilities in the long run. The early identification of an abnormal metabolic profile and altered body composition and the correction of unhealthy behaviors (such as reduced physical activity (PA), a sedentary lifestyle, and unhealthy eating) among survivors have the potential to prevent or delay late morbidity. We present a protocol for a complex evaluation of cardiometabolic risk, body composition, and bone health in children and adolescents in long-term ALL remission. In the context of a case-control study we assessed MetS and traditional cardiovascular disease risk factors, including Pathobiological Determinants of Atherosclerosis in Youth (PDAY) scores; we used anthropometric parameters (BMI, waist circumference) and a direct measuring of the fat mass and its distribution (Dual-energy X-ray Absorptiometry, DEXA) to evaluate obesity; DEXA to assess the muscle mass, and appendicular muscle mass and bone mineral density. We analy z ed survivors` PA, screen time and mean calorie intake and nutritional model using questionnaires (including the Godin Leisure-Time Physical Activity Questionnaire) and semi-structured interviews. The application of such a complex approach helps the timely identification of survivors at risk and can guide early intervention at an individual level. A broader study conducted in all three national pediatric hematology centers would allow for a more precise understanding of the problems this target group experiences and could help develop a unified approach to their solution.

Increased Female Athlete Triad Knowledge Following a Brief Video Educational Intervention

To assess female high school athletes’ changes in Female Athlete Triad (Triad) knowledge following a brief educational intervention.Triad knowledge questionnaires were completed by female high school athletes before and after either an educational video intervention or control group activities.Four high schools in the Pacific Northwest.Ninety-three female high school athletes (15.9±1.2 years) participating in basketball, cheerleading, track & field, softball, soccer, golf, tennis, and volleyball.The 10-minute Social Cognitive Theory-based educational video highlighted Triad etiology, progression, impact on sports performance, and fueling strategies to decrease Triad risk.Triad knowledge score out of 7; proportion of participants who correctly answered each question.Mann-Whitney U tests assessed differences in pre and post intervention Triad knowledge scores between the control and intervention group. The McNemar test compared the proportion of participants (intervention group) who correctly answered individual Triad knowledge questions pre vs. post-intervention.Participants in the intervention group achieved greater increases in Triad knowledge following the intervention, than did control participants (P<0.001). For each Triad question, improvements in the proportion of participants (intervention group) who answered correctly was observed (P<0.05).The Triad educational video was an effective and timeefficient method for increasing Triad knowledge among female high school athletes.