Associations of residential greenness with bone mineral density and osteoporosis: the modifying effect of genetic susceptibility.

OBJECTIVES: To investigate the associations of residential greenness with bone mineral density and incident osteoporosis, and further evaluate the potential modifying effect of genetic susceptibility. METHODS: We used the Normalised Difference Vegetation Index (NDVI) at various buffer distances, including 300 m (NDVI300m), 500 m (NDVI500m), 1000 m (NDVI1000m) and 1500 m (NDVI1500m), to serve as indicators of greenness. We fitted linear regression, logistic regression and Cox proportional hazard models to assess the associations of residential greenness with estimated bone mineral density (eBMD), prevalent osteoporosis and incident osteoporosis, respectively. With the Polygenic Risk Score (PRS) for osteoporosis, we further assessed the joint effects of genetic risk and greenness on the risk of osteoporosis. We conducted causal mediation analyses to explore potential mediators. RESULTS: Each IQR increase in NDVI300m was associated with 0.0007 (95% CI 0.0002 to 0.0013) increase in eBMD, 6% lower risk of prevalent osteoporosis (OR 0.94; 95% CI 0.92 to 0.97) and 5% lower risk of incident osteoporosis (HR 0.95; 95% CI 0.93 to 0.98). The joint effects of greenness and PRS on the risk of osteoporosis displayed a clear dose-response pattern. Compared with individuals exposed to low NDVI levels and high genetic risk, those exposed to high NDVI levels and low genetic risk had a 56% (95% CI 51% to 61%) lower risk of osteoporosis. The primary mediators in the association between greenness and incident osteoporosis were identified as PM2.5 and NO2. CONCLUSIONS: Residential greenness was associated with higher bone mineral density and decreased risk of incident osteoporosis.

Itaconate is a metabolic regulator of bone formation in homeostasis and arthritis.

OBJECTIVES: Bone remodelling is a highly dynamic process dependent on the precise coordination of osteoblasts and haematopoietic-cell derived osteoclasts. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis. METHODS: We metabolically and transcriptionally profiled cells during osteoclast and osteoblast generation. Individual gene expression was characterised by quantitative PCR and western blot. Osteoblast function was assessed by Alizarin red staining. immunoresponsive gene 1 (Irg1)-deficient mice were used in various inflammatory or non-inflammatory models of bone loss. Tissue gene expression was analysed by RNA in situ hybridisation. RESULTS: We show that during differentiation preosteoclasts rearrange their tricarboxylic acid cycle, a process crucially depending on both glucose and glutamine. This rearrangement is characterised by the induction of Irg1 and production of itaconate, which accumulates intracellularly and extracellularly. While the IRG1-itaconate axis is dispensable for osteoclast generation in vitro and in vivo, we demonstrate that itaconate stimulates osteoblasts by accelerating osteogenic differentiation in both human and murine cells. This enhanced osteogenic differentiation is accompanied by reduced proliferation and altered metabolism. Additionally, supplementation of itaconate increases bone formation by boosting osteoblast activity in mice. Conversely, Irg1-deficient mice exhibit decreased bone mass and have reduced osteoproliferative lesions in experimental arthritis. CONCLUSION: In summary, we identify itaconate, generated as a result of the metabolic rewiring during osteoclast differentiation, as a previously unrecognised regulator of osteoblasts.

Acod1-mediated inhibition of aerobic glycolysis suppresses osteoclast differentiation and attenuates bone erosion in arthritis.

OBJECTIVES: Metabolic changes are crucially involved in osteoclast development and may contribute to bone degradation in rheumatoid arthritis (RA). The enzyme aconitate decarboxylase 1 (Acod1) is known to link the cellular function of monocyte-derived macrophages to their metabolic status. As osteoclasts derive from the monocyte lineage, we hypothesised a role for Acod1 and its metabolite itaconate in osteoclast differentiation and arthritis-associated bone loss. METHODS: Itaconate levels were measured in human peripheral blood mononuclear cells (PBMCs) of patients with RA and healthy controls by mass spectrometry. Human and murine osteoclasts were treated with the itaconate derivative 4-octyl-itaconate (4-OI) in vitro. We examined the impact of Acod1-deficiency and 4-OI treatment on bone erosion in mice using K/BxN serum-induced arthritis and human TNF transgenic (hTNFtg) mice. SCENITH and extracellular flux analyses were used to evaluate the metabolic activity of osteoclasts and osteoclast progenitors. Acod1-dependent and itaconate-dependent changes in the osteoclast transcriptome were identified by RNA sequencing. CRISPR/Cas9 gene editing was used to investigate the role of hypoxia-inducible factor (Hif)-1α in Acod1-mediated regulation of osteoclast development. RESULTS: Itaconate levels in PBMCs from patients with RA were inversely correlated with disease activity. Acod1-deficient mice exhibited increased osteoclast numbers and bone erosion in experimental arthritis while 4-OI treatment alleviated inflammatory bone loss in vivo and inhibited human and murine osteoclast differentiation in vitro. Mechanistically, Acod1 suppressed osteoclast differentiation by inhibiting succinate dehydrogenase-dependent production of reactive oxygen species and Hif1α-mediated induction of aerobic glycolysis. CONCLUSION: Acod1 and itaconate are crucial regulators of osteoclast differentiation and bone loss in inflammatory arthritis.

Characteristics of bone mineral density in patients with functional hypothalamic amenorrhoea and its association with reproductive hormones and body composition.

OBJECTIVE: Bone mineral density (BMD) is typically reduced in patients with female athlete triad (FAT) and anorexia nervosa (AN). However, bone health in most patients with functional hypothalamic amenorrhoea (FHA), who may not suffer from severe energy deficiency, has not received adequate attention in clinical practice. This study aimed to investigate BMD and its association with clinical and endocrine features in individuals with FHA and to provide clinical evidence for improving bone loss and preventing osteoporosis in FHA. DESIGN: To assess the bone status of patients with FHA and investigate its association with various clinical and endocrinological characteristics. PATIENTS: We retrospectively analysed 80 patients with FHA who attended the Obstetrics and Gynecology Hospital of Fudan University from January 2022 to March 2023. MEASUREMENTS: The levels of reproductive hormones, including luteinising hormone (LH), follicle-stimulating hormone, oestradiol (E2 ) and total testosterone (TT), were examined at the time of initial diagnosis, and a body composition analyser was used to measure body fat percentage (BF%), lean body mass (LBM) and segmental muscle/fat. Dual-emission X-ray absorptiometry was used to measure lumbar spine BMD and femoral neck BMD in patients with FHA, and the Z score was calculated. RESULTS: The study cohort consisted of 80 female patients with FHA. The average age of the patients was 24.64 ± 6.02 years, and their body mass index (BMI) was 19.47 ± 2.86 kg/m2 . The duration of weight loss was 12 (6, 24) months, while the duration of oligo/amenorrhoea was 12 (4.5, 24) months. The mean degree of weight loss was 18.39 ± 9.53%. Low BMD were present in 15% of patients with FHA at the lumbar spine and/or femoral neck; 12.5% and 10% had low bone mass at the lumbar spine and femoral neck, respectively. The low bone mass group experienced a longer period of weight loss than the normal group [24 (16.5, 60) vs. 12 (4.5, 24) months, p = .037]. In addition, the abnormal group had a lower BMR (basal metabolic rate, BMR) [1158 ± 85 vs. 1231 ± 91 kcal/day, p = .011] and lower bone mineral content [2.15 ± 0.26 vs. 2.43 ± 0.31 kg, p = .009] than the normal group. Both LBMD and femoral neck BMD (Fn BMD) were positively correlated with BMI, BF%, LBM, and regional muscle/fat mass (all p < .05). There was also a positive correlation between LBMD and basal LH levels (p = .009) and waist-to-hip ratio (p = .034), whereas Fn BMD was positively correlated with TT levels (p = .029). Multiple linear regression analysis showed that LBM was positively associated with LBMD (ß = .007, 95% confidence interval [CI] = 0.004-0.009, p < .001), while trunk muscle mass was positively associated with Fn BMD (ß = .046, 95% CI = 0.013-0.080, p = .008). CONCLUSION: Fifteen percent of the patients with FHA exhibited low bone mass, a condition associated with prolonged weight loss. The basal LH and TT levels showed positive correlations with LBMD and Fn BMD, respectively. Meanwhile, BMR levels, BMI, BF%, and muscle mass were all positively correlated with LBMD and Fn BMD. Clinically, we should be attentive to suboptimal bone health in patients with FHA and take early screening, diagnosis and intervention measures, especially appropriate muscle mass gain, to prevent the onset of osteoporosis and fragility fractures in the long term.

A study on whether deep learning models based on CT images for bone density classification and prediction can be used for opportunistic osteoporosis screening.

This study utilized deep learning to classify osteoporosis and predict bone density using opportunistic CT scans and independently tested the models on data from different hospitals and equipment. Results showed high accuracy and strong correlation with QCT results, showing promise for expanding osteoporosis screening and reducing unnecessary radiation and costs. PURPOSE: To explore the feasibility of using deep learning to establish a model for osteoporosis classification and bone density value prediction based on opportunistic CT scans and to verify its generalization and diagnostic ability using an independent test set. METHODS: A total of 1219 cases of opportunistic CT scans were included in this study, with QCT results as the reference standard. The training set: test set: independent test set ratio was 703: 176: 340, and the independent test set data of 340 cases were from 3 different hospitals and 4 different CT scanners. The VB-Net structure automatic segmentation model was used to segment the trabecular bone, and DenseNet was used to establish a three-classification model and bone density value prediction regression model. The performance parameters of the models were calculated and evaluated. RESULTS: The ROC curves showed that the mean AUCs of the three-category classification model for categorizing cases into "normal," "osteopenia," and "osteoporosis" for the training set, test set, and independent test set were 0.999, 0.970, and 0.933, respectively. The F1 score, accuracy, precision, recall, precision, and specificity of the test set were 0.903, 0.909, 0.899, 0.908, and 0.956, respectively, and those of the independent test set were 0.798, 0.815, 0.792, 0.81, and 0.899, respectively. The MAEs of the bone density prediction regression model in the training set, test set, and independent test set were 3.15, 6.303, and 10.257, respectively, and the RMSEs were 4.127, 8.561, and 13.507, respectively. The R-squared values were 0.991, 0.962, and 0.878, respectively. The Pearson correlation coefficients were 0.996, 0.981, and 0.94, respectively, and the p values were all < 0.001. The predicted values and bone density values were highly positively correlated, and there was a significant linear relationship. CONCLUSION: Using deep learning neural networks to process opportunistic CT scan images of the body can accurately predict bone density values and perform bone density three-classification diagnosis, which can reduce the radiation risk, economic consumption, and time consumption brought by specialized bone density measurement, expand the scope of osteoporosis screening, and have broad application prospects.

The yield of routine laboratory examination in osteoporosis evaluation in primary care.

This study evaluated the yield of routine laboratory examination in a large population of older women in primary care. The prevalence of laboratory abnormalities was low and the clinical consequences in follow-up were limited. There was a weak association of laboratory abnormalities with osteoporosis but no association with vertebral fractures and recent fractures. PURPOSE: Most osteoporosis guidelines advice routine laboratory examination. We have investigated the yield of laboratory examinations in facture risk evaluation of elderly women in primary care. METHODS: We assessed the prevalence of laboratory abnormalities and their association with risk factors for fractures, recent fractures, low bone mineral density (BMD), and prevalent vertebral fracture in 8996 women ≥ 65 years of age participating in a primary care fracture risk screening study. In a sample of 2208 of these participants, we also evaluated the medical consequences in the medical records during a follow-up period of ≥ 1 year. RESULTS: Vitamin D deficiency (< 30 nmol/L) was present in 13% and insufficiency (< 50 nmol/L) in 43% of the study sample. The prevalence of other laboratory abnormalities (ESR, calcium, creatinine, FT4) was 4.6% in women with risk factors for fractures, 6.1% in women with low BMD (T-score ≤ - 2.5), 6.0% after a prevalent vertebral fracture, 5.2% after a recent fracture and 2.6% in the absence of important risk factors for fractures. Laboratory abnormalities other than vitamin D were associated with low BMD (OR 1.4, 95%CI 1.1-1.8) but not with prevalent vertebral fractures nor recent fractures. Low BMD was associated with renal failure (OR 2.0, 95%CI 1.3-3.4), vitamin D insufficiency (OR 1.2, 95%CI 1.0-1.3) and deficiency (OR 1.3, 95%CI 1.1-.5). In the follow-up period, 82% of the laboratory abnormalities did not result in a new diagnosis or treatment reported in the medical records. CONCLUSIONS: We identified a low prevalence of laboratory abnormalities in a primary care population of older women and the majority of these findings had no medical consequences.

Damaged bone microarchitecture by Trabecular Bone Score (TBS) and low appendicular muscle mass: main risk factors for vertebral and non-vertebral fractures in women with long-standing rheumatoid arthritis.

We ascertained the fracture risk factors stratified by vertebral and non-vertebral sites in rheumatoid arthritis (RA) females. Bone/muscle features, but not disease activity, were the main markers for fractures in this long-standing RA population: low trabecular bone score (TBS) for vertebral fracture and decreased appendicular muscle mass for non-vertebral fracture. PURPOSE: To assess risk factors for fractures, including clinical, laboratory and dual energy X-ray absorptiometry (DXA) parameters (bone mass, trabecular bone score-TBS, muscle mass) in women with established rheumatoid arthritis (RA). METHODS: Three hundred females with RA (ACR, 2010) were studied. Clinical data were obtained by questionnaire and disease activity by composite indices (DAS28, CDAI, SDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Bone mineral density (BMD), TBS, body composition and Vertebral Fracture Assessment (VFA) were performed by DXA. Logistic regression models were constructed to identify factors independently associated with vertebral (VF) and non-vertebral fractures (NVF), separately. RESULTS: Through rigorous eligibility criteria, a total of 265 women were yielded for final data analysis (median age, 55 [22-86] years; mean disease duration, 16.2 years). Prevalence of VF and NVF were 30.6% and 17.4%, respectively. In multivariate analyzes, TBS (OR = 1.6, 95%CI = 1.09-2.36, p = 0.017), CRP (OR = 1.54, 95%CI = 1.15-2.08, p = 0.004), and parathormone (OR = 1.24, 95%CI = 1.05-1.45, p = 0.009) were risk factors for VF, whereas low appendicular muscle mass (OR = 2.71; 95%CI = 1.01-7,28; p = 0.048), body mass index (BMI) (OR = 0.90, 95%CI = 0.82-0.99; p = 0.025), ESR (OR = 1.18, 95%CI = 1.01-1,38, p = 0,038) and hip BMD (OR = 1.82, 95%CI = 1.10-3.03, p = 0.02) were associated with NVF. CONCLUSION: In women with long-term RA, markers of fractures differed between distinct skeletal sites (vertebral and non-vertebral). The magnitude of association of bone/muscle parameters with fracture (TBS for VF and appendicular muscle mass for NVF) was greater than that of the association between RA activity and fracture. TBS seems to have greater discriminative power than BMD to identify subjects with VF in long-standing RA.

Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (- 0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.

Trabecular bone volume fraction in Holocene and Late Pleistocene humans.

Research suggests that recent modern humans have gracile skeletons in having low trabecular bone volume fraction (BV/TV) and that gracilization of the skeleton occurred in the last 10,000 years. This has been attributed to a reduction in physical activity in the Holocene. However, there has been no thorough sampling of BV/TV in Pleistocene humans due to limited access to high resolution images of fossil specimens. Therefore, our study investigates the gracilization of BV/TV in Late Pleistocene humans and recent (Holocene) modern humans to improve our understanding of the emergence of gracility. We used microcomputed tomography to measure BV/TV in the femora, humeri and metacarpals of a sample of Late Pleistocene humans from Dolní Vestonice (Czech Republic, ∼26 ka, n = 6) and Ohalo II (Israel, ∼19 ka, n = 1), and a sample of recent humans including farming groups (n = 39) and hunter-gatherers (n = 6). We predicted that 1) Late Pleistocene humans would exhibit greater femoral and humeral head BV/TV compared with recent humans and 2) among recent humans, metacarpal head BV/TV would be greater in hunter-gatherers compared with farmers. Late Pleistocene humans had higher BV/TV compared with recent humans in both the femur and humerus, supporting our first prediction, and consistent with previous findings that Late Pleistocene humans are robust as compared to recent humans. However, among recent humans, there was no significant difference in BV/TV in the metacarpals between the two subsistence groups. The results highlight the similarity in BV/TV in the hand of two human groups from different geographic locales and subsistence patterns and raise questions about assumptions of activity levels in archaeological populations and their relationships to trabecular BV/TV.

Bone health in SATB2-associated syndrome: Results from a large prospective cohort and recommendations for surveillance.

Alterations in SATB2 result in SATB2-associated syndrome (SAS; Glass syndrome, OMIM 612313), an autosomal dominant multisystemic disorder predominantly characterized by developmental delay, craniofacial anomalies, and growth retardation. The bone phenotype of SAS has been less explored until recently and includes a variety of skeletal deformities, increased risk of low bone mineral density (BMD) with a propensity to fractures, and other biochemical abnormalities that suggest elevated bone turnover. We present the results of ongoing surveillance of bone health from 32 individuals (47% females, 3-18 years) with molecularly-confirmed SAS evaluated at a multidisciplinary clinic. Five individuals (5/32, 16%) were documented to have BMD Z-scores by DXA scans of -2.0 SD or lower and 7 more (7/32, 22%) had Z-scores between -1 and - 2 SD at the lumbar spine or the total hip. Alkaline phosphatase levels were found to be elevated in 19 individuals (19/30, 63%) and determined to correspond to bone-specific alkaline phosphatase elevations when measured (11/11, 100%). C-telopeptide levels were found to be elevated when adjusted by age and gender in 6 individuals (6/14, 43%). Additionally, the two individuals who underwent bone cross-sectional geometry evaluation by peripheral quantitative computed tomography were documented to have low cortical bone density for age and sex despite concurrent DXA scans that did not have this level of decreased density. While we could not identify particular biochemical abnormalities that predicted low BMD, the frequent elevations in markers of bone formation and resorption further confirmed the increased bone turnover in SAS. Based on our results and other recently published studies, we propose surveillance guidelines for the skeletal phenotype of SAS.

Efficacy, tolerability, and bone density outcomes of elagolix with add-back therapy for endometriosis-associated pain: 12 months of an ongoing randomized phase 3 trial.

BACKGROUND: Elagolix, an approved oral treatment for endometriosis-associated pain, has been associated with hypoestrogenic effects when used as monotherapy. Hormonal add-back therapy has the potential to mitigate these effects. OBJECTIVE: To evaluate efficacy, tolerability, and bone density outcomes of elagolix 200 mg twice daily with 1 mg estradiol /0.5 mg norethindrone acetate (add-back) therapy once daily compared with placebo in premenopausal women with moderate-to-severe endometriosis-associated pain. STUDY DESIGN: This ongoing, 48-month, phase 3 study consists of a 12-month, double-blind period, with randomization 4:1:2 to elagolix 200 mg twice daily with add-back therapy, elagolix 200 mg twice daily monotherapy for 6 months followed by elagolix with add-back therapy, or placebo. The co-primary endpoints were proportion of patients with clinical improvement (termed "responders") in dysmenorrhea and nonmenstrual pelvic pain at month 6. We report 12-month results on efficacy of elagolix with add-back therapy versus placebo in reducing dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and fatigue. Tolerability assessments include adverse events and change from baseline in bone mineral density. RESULTS: A total of 679 patients were randomized to elagolix with add-back therapy (n=389), elagolix monotherapy (n=97), or placebo (n=193). Compared with patients randomized to placebo, a significantly greater proportion of patients randomized to elagolix with add-back therapy responded with clinical improvement in dysmenorrhea (62.8% versus 23.7%; P≤.001) and nonmenstrual pelvic pain (51.3% versus 36.8%; P≤.001) at 6 months. Compared with placebo, elagolix with add-back therapy produced significantly greater improvement from baseline in 7 hierarchically ranked secondary endpoints including dysmenorrhea (months 12, 6, 3), nonmenstrual pelvic pain (months 12, 6, 3), and fatigue (months 6) (all P<.01). Overall, the incidence of adverse events was 73.8% with elagolix plus add-back therapy and 66.8% with placebo. The rate of severe and serious adverse events did not meaningfully differ between treatment groups. Study drug discontinuations associated with adverse events were low in patients receiving elagolix with add-back therapy (12.6%) and those receiving placebo (9.8%). Patients randomized to elagolix monotherapy exhibited decreases from baseline in bone mineral density of -2.43% (lumbar spine), -1.54% (total hip), and -1.78% (femoral neck) at month 6. When add-back therapy was added to elagolix at month 6, the change from baseline in bone mineral density remained in a similar range of -1.58% to -1.83% at month 12. However, patients who received elagolix plus add-back therapy from baseline exhibited little change from baseline in bone mineral density (<1% change) at months 6 and 12. CONCLUSION: Compared with placebo, elagolix with add-back therapy resulted in significant, clinically meaningful improvement in dysmenorrhea, nonmenstrual pelvic pain, and fatigue at 6 months that continued until month 12 for both dysmenorrhea and nonmenstrual pelvic pain. Elagolix with add-back therapy was generally well tolerated. Loss of bone mineral density at 12 months was greater in patients who received elagolix with add-back therapy than those who received placebo. However, the change in bone mineral density with elagolix plus add-back therapy was < 1% and was attenuated compared with bone loss observed with elagolix monotherapy.

Longitudinal MR-based proton-density fat fraction (PDFF) and T2* for the assessment of associations between bone marrow changes and myelotoxic chemotherapy.

OBJECTIVES: MR imaging-based proton density fat fraction (PDFF) and T2* imaging has shown to be useful for the evaluation of degenerative changes in the spine. Therefore, the aim of this study was to investigate the influence of myelotoxic chemotherapy on the PDFF and T2* of the thoracolumbar spine in comparison to changes in bone mineral density (BMD). METHODS: In this study, 19 patients were included who had received myelotoxic chemotherapy (MC) and had received a MR imaging scan of the thoracolumbar vertebrates before and after the MC. Every patient was matched for age, sex, and time between the MRI scans to two controls without MC. All patients underwent 3-T MR imaging including the thoracolumbar spine comprising chemical shift encoding-based water-fat imaging to extract PDFF and T2* maps. Moreover, trabecular BMD values were determined before and after chemotherapy. Longitudinal changes in PDFF and T2* were evaluated and compared to changes in BMD. RESULTS: Absolute mean differences of PDFF values between scans before and after MC were at 8.7% (p = 0.01) and at -0.5% (p = 0.57) in the control group, resulting in significantly higher changes in PDFF in patients with MC (p = 0.008). BMD and T2* values neither showed significant changes in patients with nor in those without myelotoxic chemotherapy (p = 0.15 and p = 0.47). There was an inverse, yet non-significant correlation between changes in PDFF and BMD found in patients with myelotoxic chemotherapy (r = -0.41, p = 0.12). CONCLUSION: Therefore, PDFF could be a useful non-invasive biomarker in order to detect changes in the bone marrow in patients receiving myelotoxic therapy. CLINICAL RELEVANCE STATEMENT: Using PDFF as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment may help enable more targeted countermeasures at commencing states of bone marrow degradation and reduce risks of possible fragility fractures. KEY POINTS: Quantifying changes in bone marrow fat fraction, as well as T2* caused by myelotoxic pharmaceuticals using proton density fat fraction, is feasible. Proton density fat fraction could potentially be established as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment.

Lithium use and bone health in women with bipolar disorder: A cross-sectional study.

INTRODUCTION: Several psychiatric disorders and medications used to treat them appear to be independently associated with skeletal deficits. As there is increasing evidence that lithium possesses skeletal protective properties, we aimed to investigate the association between lithium use and bone health in a group of women with bipolar disorder. METHOD: Women with bipolar disorder (n = 117, 20+ years) were recruited from south-eastern Australia. Bipolar disorder was confirmed using a clinical interview (SCID-I/NP). Bone mineral density (BMD; g/cm2 ) was measured at the spine, hip and total body using dual-energy x-ray absorptiometry and low bone mass determined by BMD T-score of <-1.0. Weight and height were measured, socioeconomic status (SES) determined and information on medication use and lifestyle factors self-reported. Linear and logistic regression were used to test associations between lithium and (i) BMD and (ii) low bone mass, respectively. RESULTS: Thirty-five (29.9%) women reported current lithium use. Lithium users and non-users differed in regard to SES and BMD; otherwise, groups were similar. After adjustments, mean BMD among lithium users was 5.1% greater at the spine (1.275 [95% CI 1.229-1.321] vs. 1.214 [1.183-1.244] g/cm2 , p = 0.03), 4.2% greater at the total hip (0.979 [0.942-1.016] vs. 0.938 [0.910-0.966] g/cm2 , p = 0.03) and 2.2% greater at the total body (1.176 [1.148-1.205] vs. 1.150 [1.129-1.171] g/cm2 , p = 0.08) compared to participants not receiving lithium. Lithium users were also less likely to have low bone mass (22.9% vs. 43.9%, p = 0.031). Associations persisted after adjustment for confounders. CONCLUSION: These data suggest lithium is associated with greater BMD and reduced risk of low bone mass in women with bipolar disorder. Research into the underlying mechanisms is warranted.

Preservation of fat mass at the expense of lean mass in children with end-stage chronic liver disease.

BACKGROUND: Sarcopenia predicts morbidity and mortality in end-stage chronic liver disease (ESCLD). Here, we describe changes in body composition in children with ESCLD before and after liver transplantation (LT). METHODS: Retrospective analysis of whole body DXA scans performed before and after LT over 4 years. Appendicular and whole-body fat mass and lean mass were expressed as fat mass (FMI) and lean mass (LMI) index z-scores. Sarcopenia was defined as leg LMI z-score <-1.96. RESULTS: Eighty-three DXA scans of children before or after LT were studied. Sarcopenia had a positive correlation with weight (0.8, p < .01), height (0.48, p < .05), and BMI z-score (0.77, p < .01), as well as arm, trunk, and total mean mass indices. It correlated negatively with indices of hypersplenism: PLTs (-0.57, p < .01), Neu (-0.50, p < .05), WCC (-0.44, p < .05), and days to discharge (-0.46, p < .05). At baseline: 13/25 (52%) children were sarcopenic and stayed in the hospital after LT for longer. Eight were stunted with a higher WCC and Ne/Ly ratio. All had normal FM indices. One year after LT, 12/26 children remained sarcopenic. Seven were stunted. Two years after LT, 5/15 were sarcopenic, and 5 were stunted. Three years after LT, 1/10 was sarcopenic, and 2 were stunted. By 4 years after LT, 1/7 was sarcopenic, and the same one was stunted. FM indices remained normal. CONCLUSIONS: Sarcopenic patients stayed longer in the hospital after LT. Lean mass indices were mostly within the normal range by 4 years after LT. 32% of children were stunted, and markers of inflammation were correlated with stunting. Fat mass was preserved at the cost of lean mass.

Hypopituitarism and bone disease: pathophysiology, diagnosis and treatment outcomes.

Hypopituitarism is a rare but significant endocrine disorder characterized by the inadequate secretion of one or more pituitary hormones. The intricate relationship between hypopituitarism and bone health is a topic of growing interest in the medical community. In this review the authors explore associations between hypopituitarism and bone health, with specific examination of the impact of growth hormone deficiency, central hypogonadism, central hypocortisolism, and central hypothyroidism. Pathogenesis, diagnosis, and treatment options as well as challenges posed by osteopenia, osteoporosis, and fractures in hypopituitarism are discussed.

Endocrine consequences of breast cancer therapy and survivorship.

Breast cancer survivorship is increasing, due to earlier diagnosis of the disease and more effective therapies. Long-term endocrine sequelae, including early menopause, bone health, fertility implications and menopausal symptoms, are important survivorship issues. Ovarian failure is common with chemotherapy and options for preserving fertility in young women include ovarian suppression during chemotherapy and oocyte or embryo cryopreservation before chemotherapy. Tamoxifen as adjunct therapy in premenopausal women leads to ovarian stimulation, sometimes ovulation and occasionally pregnancy with important teratogenic implications. Aromatase inhibitor therapy with or without gonadotrophin releasing hormone (GnRH) agonist leads to profound bone loss and anti-resorptive therapy is advised to prevent fracture. Tamoxifen acts to preserve bone in postmenopausal women but not premenopausal women. Pregnancy is not discouraged in young women with early breast cancer, even to the point of pausing adjunct therapy in order to conceive. However, menopausal hormone therapy is discouraged even years later. Non-hormonal therapy for menopausal symptoms in breast cancer survivors is available but, in some cases, estrogen-containing therapy may be worthy of consideration for quality of life in the informed patient.

Radiographic alveolar bone assessment in correlation with primary implant stability: A systematic review and meta-analysis.

INTRODUCTION: The radiographic examination of alveolar bone using 3D radiographic examination is essential in dental implant treatment planning. Our study aimed to systematically review and quantitatively analyze the correlation between alveolar bone parameters, specifically bone density and cortical bone thickness, assessed using cone beam computed tomography (CBCT) and/or multidetector computed tomography (MDCT); and primary implant stability (PIS) determined using implant stability quotient (ISQ), Periotest® value (PTV), and insertion torque value (ITV). METHODS: This review was registered in the PROSPERO database (registration number CRD42022307245). An electronic literature search was conducted on the PubMed, SCOPUS, and Web of Science databases for papers published until February 2022. The Quality Assessment in Prognostic Studies (QUIPS) tool was used to assess risk of bias. Meta-analyses were conducted to calculate the estimated average correlation coefficient based on a multilevel random-effects model, followed by subgroup analysis. RESULTS: Twenty-six studies were included in this review, consisting of 17 prospective cohort studies, eight retrospective cohort studies, and one nonrandomized controlled trial. A total of 3109 implants placed in 1171 subjects were analyzed. Twenty-three studies were evaluated using meta-analysis. The alveolar bone condition was significantly correlated with ISQ (r = 0.60; p < .001), IT (r = 0.52; p < .001), and PTV (r = -0.42; p < .05). CONCLUSION: Alveolar bone condition is significantly associated with PIS. Low bone density and thin cortical bone can lead to low PIS; therefore, modification of treatment planning and surgical procedures might be needed to avoid poor osseointegration.

Recognizing bisphosphonate-induced ear osteonecrosis in primary care: a case report.

INTRODUCTION: Medication-related ear canal osteonecrosis (MRECO) is a growing concern linked to prolonged anti-resorptive medication use. Despite primary care providers being key prescribers of these medications, there is limited information about MRECO in primary care literature. This article presents a case of bisphosphonate-induced osteonecrosis of the external auditory canal (EAC), emphasizing the vital role of primary care providers in identifying this rare yet significant side effect of anti-resorptive medication. MAIN SYMPTOMS AND CLINICAL FINDINGS: A 65-year-old female, on long-term alendronic acid for osteoporosis, presented to primary care with a 2-year history of left-sided ear blockage and itchiness. Despite prolonged topical treatment for ear wax, symptoms persisted, leading to an Otolaryngology referral. Microsuction revealed exposed bone in the left EAC. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: A computed tomography scan confirmed bony erosion of the left EAC, and in the absence of other osteonecrosis risk factors, bisphosphonate-induced osteonecrosis was diagnosed. Management involved bisphosphonate discontinuation, regular aural toilet, and topical treatment, achieving complete ear canal epithelialisation within 6 months. CONCLUSION: MRECO, a rare complication of anti-resorptive therapy, is anticipated to rise with increasing antiresorptive medication use in the ageing population. Unexplained ear symptoms in those with a history of current or prior anti-resorptive therapy should raise clinical concern, prompting evaluation for exposed bone in the EAC. Raising awareness of MRECO among primary care providers is crucial for early diagnosis and timely management.

Bone Mineral Density Derived from Cardiac CT Scans: Using Contrast Enhanced Scans for Opportunistic Screening.

PURPOSE: Osteoporosis is under-diagnosed and often co-exists with other diseases. Very low bone mineral density (BMD) indicates risk of osteoporosis and opportunistic screening for low BMD in CT-scans has been suggested. In a non-contrast enhanced thoracic CT scan, the scan-field-of-view includes vertebrae enabling BMD estimation. However, many CT scans are obtained by administration of contrast material. If the impact of contrast enhancement on BMD measurements could be quantified, considerably more patients are eligible for screening. METHODS: This study investigated the impact of intravenous contrast on thoracic BMD measurements in cardiac CT scans pre- and post-contrast, including different contrast trigger levels of 130 and 180 Hounsfield units (HU). BMD was measured using quantitative CT with asynchronous calibration. RESULTS: In 195 participants undergoing cardiac CT (mean age 57±9 years, 37 % females) contrast increased mean thoracic BMD from 116±33 mg/cm3 (non-enhanced CT) to 130±38 mg/cm3 (contrast-enhanced CT) (p<0.001). Using clinical cut-off values for very low (<80 mg/cm3) and low BMD (<120 mg/cm3) showed that 24 % (47/195 participants) were misclassified when BMD was measured on contrast-enhanced CT-scans. Of the misclassified patients, 6 % (12/195 participants) were categorized as having low BMD despite having very low BMD on the non-enhanced images. Contrast-CT using a higher contrast trigger level showed a significant increase in BMD compared to the lower trigger level (119±32 vs. 135±40 mg/cm3, p<0.01). CONCLUSION: For patients undergoing cardiac CT, using contrast-enhanced images to assess BMD entails substantial overestimation. Contrast protocol trigger levels also affect BMD measurements. Adjusting for these factors is needed before contrast-enhanced images can be used clinically. MINI ABSTRACT: Osteoporosis is under-diagnosed. Contrast-enhanced CT made to examine other diseases might be utilized simultaneously for bone mineral density (BMD) screening. These scans, however, likely entails overestimation of BMD due to the effect of contrast. Adjusting for this effect is needed before contrast-enhanced images can be implemented clinically for BMD screening.

Two Pathological Fractures in a Patient with Chronic Abnormalities in Serum Markers Following Two Liver Transplantations: A Case Report and Literature Review.

Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.