Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study.

Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. PURPOSE: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. METHODS: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. RESULTS: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. CONCLUSION: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF.

Trabecular bone mineral density as measured by thoracic vertebrae predicts incident hip and vertebral fractures: the multi-ethnic study of atherosclerosis.

We evaluated the relationship of bone mineral density (BMD) by computed tomography (CT), to predict fractures in a multi-ethnic population. We demonstrated that vertebral and hip fractures were more likely in those patients with low BMD. This is one of the first studies to demonstrate that CT BMD derived from thoracic vertebrae can predict future hip and vertebral fractures. PURPOSE/INTRODUCTION: Osteoporosis affects an enormous number of patients, of all races and both sexes, and its prevalence increases as the population ages. Few studies have evaluated the association between the vertebral trabecular bone mineral density(vBMD) and osteoporosis-related hip fracture in a multiethnic population, and no studies have demonstrated the predictive value of vBMD for fractures. METHOD: We sought to determine the predictive value of QCT-based trabecular vBMD of thoracic vertebrae derived from coronary artery calcium scan for hip fractures in the Multi-Ethnic Study of Atherosclerosis(MESA), a nationwide multicenter cohort included 6814 people from six medical centers across the USA and assess if low bone density by QCT can predict future fractures. Measures were done using trabecular bone measures, adjusted for individual patients, from three consecutive thoracic vertebrae (BDI Inc, Manhattan Beach CA, USA) from non-contrast cardiac CT scans. RESULTS: Six thousand eight hundred fourteen MESA baseline participants were included with a mean age of 62.2 ± 10.2 years, and 52.8% were women. The mean thoracic BMD is 162.6 ± 46.8 mg/cm3 (95% CI 161.5, 163.7), and 27.6% of participants (n = 1883) had osteoporosis (T-score 2.5 or lower). Over a median follow-up of 17.4 years, Caucasians have a higher rate of vertebral fractures (6.9%), followed by Blacks (4.4%), Hispanics (3.7%), and Chinese (3.0%). Hip fracture patients had a lower baseline vBMD as measured by QCT than the non-hip fracture group by 13.6 mg/cm3 [P < 0.001]. The same pattern was seen in the vertebral fracture population, where the mean BMD was substantially lower 18.3 mg/cm3 [P < 0.001] than in the non-vertebral fracture population. Notably, the above substantial relationship was unaffected by age, gender, race, BMI, hypertension, current smoking, medication use, or activity. Patients with low trabecular BMD of thoracic vertebrae showed a 1.57-fold greater risk of first hip fracture (HR 1.57, 95% CI 1.38-1.95) and a nearly threefold increased risk of first vertebral fracture (HR 2.93, 95% CI 1.87-4.59) compared to normal BMD patients. CONCLUSION: There is significant correlation between thoracic trabecular BMD and the incidence of future hip and vertebral fracture. This study demonstrates that thoracic vertebrae BMD, as measured on cardiac CT (QCT), can predict both hip and vertebral fractures without additional radiation, scanning, or patient burden. Osteopenia and osteoporosis are markedly underdiagnosed. Finding occult disease affords the opportunity to treat the millions of people undergoing CT scans every year for other indications.

CT image-based biomarkers for opportunistic screening of osteoporotic fractures: a systematic review and meta-analysis.

The use of opportunistic computed tomography (CT) image-based biomarkers may be a low-cost strategy for screening older individuals at high risk for osteoporotic fractures and populations that are not sufficiently targeted. This review aimed to assess the discriminative ability of image-based biomarkers derived from existing clinical routine CT scans for hip, vertebral, and major osteoporotic fracture prediction. A systematic search in PubMed MEDLINE, Embase, Cochrane, and Web of Science was conducted from the earliest indexing date until July 2023. The evaluation of study quality was carried out using a modified Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. The primary outcome of interest was the area under the curve (AUC) and its corresponding 95% confidence intervals (CIs) obtained for four main categories of biomarkers: areal bone mineral density (BMD), image attenuation, volumetric BMD, and finite element (FE)-derived biomarkers. The meta-analyses were performed using random effects models. Sixty-one studies were included in this review, among which 35 were synthesized in a meta-analysis and the remaining articles were qualitatively synthesized. In comparison to the pooled AUC of areal BMD (0.73 [95% CI 0.71-0.75]), the pooled AUC values for predicting osteoporotic fractures for FE-derived parameters (0.77 [95% CI 0.72-0.81]; p < 0.01) and volumetric BMD (0.76 [95% CI 0.71-0.81]; p < 0.01) were significantly higher, but there was no significant difference with the pooled AUC for image attenuation (0.73 [95% CI 0.66-0.79]; p = 0.93). Compared to areal BMD, volumetric BMD and FE-derived parameters may provide a significant improvement in the discrimination of osteoporotic fractures using opportunistic CT assessments.

Low Bone Mineral Density and Risk for Osteoporotic Fractures in Patients with Chronic Pancreatitis.

Introduction: Chronic pancreatitis (CP) can lead to malnutrition, an established risk factor for low bone mineral density (BMD) and fractures. This study aims to determine the prevalence of low BMD, assess fracture incidence and explore risk factors for fractures in patients with CP. Patients and methods: We performed a retrospective analysis of all patients treated for CP at Karolinska University Hospital between January 1999 and December 2020. Electronic medical records were retrieved to assess demographic, laboratory and clinical data. Patients subjected to dual-energy X-ray absorptiometry (DXA) were categorised as either low BMD or normal BMD. We investigated whether the rate of fractures, defined by chart review, differed between these groups using Cox regression, adjusting the model for age, sex and body mass index (BMI). Additional within-group survival analysis was conducted to identify potential risk factors. Results: DXA was performed in 23% of patients with definite CP. Some 118 patients were included in the final analysis. Low BMD was present in 63 (53.4%) patients. Mean age at CP diagnosis in the total cohort was 53.1 years and was significantly lower in patients with normal BMD than in patients with low BMD (45.5 vs. 59.8, p < 0.001). Significant differences were observed in smoking status and disease aetiology, i.e., a higher proportion of patients with low BMD were current or former smokers, with nicotine or alcohol being a more common cause of CP (p < 0.05). Total follow-up time was 898 person-years. Fractures were found in 33 (28.0%) patients: in 5 of 55 patients (16.7%) with normal DXA and in 28 of 63 patients (44.4%) with low BMD (adjusted hazard ratio = 3.4, 95% confidence interval (CI) = 1.2-9.6). Patients with at least 3 months of consecutive pancreatic enzyme replacement therapy (PERT) or vitamin D treatment had a longer median time to fracture after CP diagnosis. Conclusion: DXA was only performed in 23% of patients with definite CP in this study, indicating a low adherence to current European guidelines. A low BMD was found in 53.4% of patients with CP, and 44% of the patients with a low BMD experienced a fracture during follow-up. Moreover, the fracture rate in patients with low BMD increased compared to those with normal BMD.

Pulsed Electromagnetic Field Affects the Development of Postmenopausal Osteoporotic Women with Vertebral Fractures.

BACKGROUND: Postoperative pain, dysfunction, and significant bone loss may occur after vertebral fractures, which will lead to the occurrence of refractures and shorten the survival time, so postoperative rehabilitation is very important. Pulsed electromagnetic field therapy is noninvasive, pain-relieving, and beneficial to reduce bone loss and is an important treatment for patients to recover after surgery. Therefore, this study analyzed the effect of postmenopausal women's vertebral fracture rehabilitation after pulsed electromagnetic field treatment. METHOD: This study uses a randomized controlled study, respectively, in the pulsed electromagnetic field treatment group (40 cases) and the control group (42 cases), respectively. We studied the results of health-related quality of life scores (HRQOL), back pain, body function, hip bone density, bone microstructure of tibia, and radius after 1 month and 3 months after surgery. RESULTS: Compared with the control group, the pulsed electromagnetic field treatment group (PEMF) can improve significantly the psychological score, 6-minute walk test, and Chair Sit-and-Reach one month after the operation. And at 3 months after surgery, the pulsed electromagnetic field treatment group can improve significantly in health-related quality of life scores (HRQOL), back pain, and body function. Regarding the effect of changes in bone mass, compared with the control group, pulsed electromagnetic field treatment had no significant effect on changes in hip bone density. As a result of changes in bone microstructure, pulsed electromagnetic field treatment can significantly improve the bone microstructure of the radius and tibia three months after vertebral fractures. CONCLUSION: Pulsed electromagnetic field therapy has positive significance for improving pain, body functional changes, and bone loss after vertebral fracture surgery.

Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women.

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real-world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN-BMD) were well-described by a bi-exponential relationship with first-order BMD formation (k1 ) and resorption (k2 ) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25-maximum 53]) lose 0.6% FN-BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10-year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN-BMD of 0.975 g/cm2 at menopause, associated with a 10-year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long-term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.

Finite element analysis of wedge and biconcave deformity in four different height restoration after augmentation of osteoporotic vertebral compression fractures.

PURPOSE: Biomechanical comparison of wedge and biconcave deformity of different height restoration after augmentation of osteoporotic vertebral compression fractures was analyzed by three-dimensional finite element analysis (FEA). METHODS: Three-dimensional finite element model (FEM) of T11-L2 segment was constructed from CT scan of elderly osteoporosis patient. The von Mises stresses of vertebrae, intervertebral disc, facet joints, displacement, and range of motion (ROM) of wedge and biconcave deformity were compared at four different heights (Genant 0-3 grade) after T12 vertebral augmentation. RESULTS: In wedge deformity, the stress of T12 decreased as the vertebral height in neutral position, flexion, extension, and left axial rotation, whereas increased sharply in bending at Genant 0; L1 and L2 decreased in all positions excluding flexion of L2, and T11 increased in neutral position, flexion, extension, and right axial rotation at Genant 0. No significant changes in biconcave deformity. The stress of T11-T12, T12-L1, and L1-L2 intervertebral disc gradually increased or decreased under other positions in wedge fracture, whereas L1-L2 no significant change in biconcave fracture. The utmost overall facet joint stress is at Genant 3, whereas there is no significant change under the same position in biconcave fracture. The displacement and ROM of the wedge fracture had ups and downs, while a decline in all positions excluding extension in biconcave fracture. CONCLUSIONS: The vertebral restoration height after augmentation to Genant 0 affects the von Mises stress, displacement, and ROM in wedge deformity, which may increase the risk of fracture, whereas restored or not in biconcave deformity.

Long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis: 3-year post-marketing surveillance study.

INTRODUCTION: Denosumab is a humanized IgG2 monoclonal antibody that was approved for the treatment of osteoporosis in Japan in 2013. This study aimed to investigate the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. MATERIALS AND METHODS: This 3-year, prospective, observational, post-marketing study included patients who initiated treatment with denosumab (60 mg/6 months) for osteoporosis. Data were assessed at baseline, 3, 6, 12, 24 and 36 months. Key endpoints were adverse events (AEs), adverse drug reactions (ADRs), occurrence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers. Multivariate analyses were conducted to identify predictors of hypocalcaemia and percent change in BMD. RESULTS: Overall, 3534 patients were assessed (mean 75.7 years; 89.8% women). In total, 298 patients (8.4%) developed ADRs; the most common was hypocalcaemia (3.9%). Hypocalcaemia risk was significantly increased in patients with creatinine clearance < 30 mL/min, no prior use of bisphosphonates, prior use of calcium and vitamin D preparations, baseline serum calcium < 8.5 mg/dL, and no concomitant use of calcium or vitamin D preparations. Six patients had adjudicated osteonecrosis of the jaw. Lumbar spine BMD increased significantly from baseline (mean percent change: 11.4% at 36 months). All bone turnover markers decreased significantly from baseline. Over 3 years, 3.3% of patients developed a new osteoporotic fracture. CONCLUSIONS: This study confirmed the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. No new safety signals were identified.

Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF.

CONTEXT: Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population. DESIGN: The European Calcified Tissue Society and the International Osteoporosis Foundation convened a working group to produce an updated review of literature published after 2017 on this topic. RESULTS: Fragility fractures in PW are rare and mostly due to secondary osteoporosis (ie, in presence of an underlying disease such as hormonal, inflammatory, or digestive disorders). In absence of another disorder, low bone mineral density (BMD) together with fragility fractures qualifies as idiopathic osteoporosis. In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities. BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-tumor necrosis factor alpha improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3%-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed. CONCLUSION: The majority of PW with osteoporosis have an underlying disease. Specific therapy of these diseases, as well as antiresorptive and anabolic drugs, improve BMD, but without evidence of fracture reduction.

Investigation of the Diet-Gut-Muscle Axis in the Osteoporotic Fractures in Men Study.

OBJECTIVES: To investigate the association between dietary fiber density (grams of fiber consumed per 100 kcal) with the gut-muscle axis in older adult men. DESIGN: Cross-sectional study. SETTING: Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16). PARTICIPANTS: Older adult men (average age, 85y) from the MrOS study. MEASUREMENTS: Men who were in the highest tertiles for dietary fiber density and the percentage of whole body lean mass were defined as T3T3 (n=42), whereas men who were in the lowest and intermediate tertiles for these variables were defined as T1T1 (n=32), T1T3 (n=24), and T3T1 (n=13), respectively. Additionally, measures of physical function, including the short physical performance battery (SPPB) score and grip strength were higher in T3T3 when compared with T1T1. Gut bacterial abundance was quantified with use of 16S v4 rRNA sequencing, and the bacterial functional potential was derived from the 16S data with PICRUSt. Chao1, ACE, Shannon, Simpson, and Fisher indices were used as measures of α-diversity. Weighted and unweighted Unifrac, and Bray-Curtis were used as measures of ß-diversity. Age, physical activity score, smoking, and number of medications-adjusted DESeq2 models were used to identify bacteria and functions that were different when comparing T3T3 with T1T1, but that were not also different when comparing T3T3 with T1T3 or T3T1. RESULTS: α-diversity was not different, but significant differences for ß-diversity (unweighted UniFrac, Bray-Curtis) were identified when comparing T3T3 with T1T1. Known butyrate-producing bacteria, including Ruminococcus, Lachnospira, and Clostridia, and gene counts for butyrate production (KEGG IDs: K01034, K01035) were higher in T3T3, when compared with T1T1. CONCLUSION: These data suggest that a high-fiber diet may positively impact butyrate-producing genera and gene counts, which collectively may be involved in mechanisms related to the percentage of whole body lean mass and physical functioning in older adult men. Future studies aimed at testing the causative role of this hypothesis are of interest.

Application of percutaneous vertebroplasty and percutaneous kyphoplasty in treating Kümmell's patients with different stages and postural correction status.

Objectives: To compare the effects of percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) in treating Kümmell's disease (KD) patients.Methods: This prospective cohort study involved 19 KD patients (20 involved vertebrae). The surgical selection was dependent on clinical stages and postural correction status. The status of vertebral reduction, amount of cement injection, and amount of cement leakage during the surgery were recorded. The anterior vertebral height and kyphotic angle were measured by X-ray scan. The degree of low back pain and the quality of life were assessed by the visual analog scale and Oswestry disability index, respectively.Results: On the third-day post-operation and the last follow-up, anterior vertebral height was increased, kyphosis angle was reduced, low back pain was relieved, and life quality was improved in both groups compared with pre-operation. There was no significant difference between the two groups in cement amount, cement leakage rate, vertebral height correction, and kyphotic correction angle. The nerve function of stage III patients with spinal cord injury was improved from a Frankel grade D to E.Expert Opinion: PVP and PKP could be used in treating KD patients, and the surgical selection could be dependent on the clinical stages and status of postural correction.Conclusion: PVP and PKP could be used in treating KD patients, and the surgical selection could be dependent on the clinical stages and status of postural correction.

Age related changes in the bone microstructure in patients with femoral neck fractures.

BACKGROUND: The risk of femoral neck fracture progressively increases with age. However, the reasons behind this consistent increase in the fracture risk can't be completely justified by the decrease in the bone mineral density. The objective of this study was to analyze the correlation between various bone structural features and age. STUDY DESIGN & METHODS: A total of 29 consecutive patients who suffered an intracapsular hip fracture and underwent joint replacement surgery between May 2012 and March 2013 were included in this study. A 2 cm × 1 cm Ø cylindrical trabecular bone sample was collected from the femoral heads and preserved in formaldehyde. Bone mineral density (BMD), microarchitecture, organic content and crystallography were analyzed using a Dual-energy X-ray absorptiometry scan, micro-CT scan, and high resolution magic-angle-spinning-nuclear magnetic resonance (MAS-NMR), respectively. Statistical correlations were made using Spearman´s or Pearson´s correlation tests depending on the distribution of the continuous variables. RESULTS: The mean patient age was 79.83 ± 9.31 years. A moderate negative correlation was observed between age and the hydrogen content in bone (1H), which is an indirect estimate to quantify the organic matrix (r = -0.512, p = 0.005). No correlations were observed between BMD, trabecular number, trabecular thickness, phosphorous content, apatite crystal size, and age (r = 0.06, p = 0.755; r = -0.008, p = 0.967; r = -0.046, p = 0.812; r = -0.152, p = 0.430, respectively). A weak positive correlation was observed between Charlson´s comorbidity index (CCI) and c-axis of the hydroxiapatite (HA) crystals (r = -0.400, p = 0.035). CONCLUSION: The femoral head relative protein content progressively decreases with age. BMD was not correlated with other structural bone parameters and age. Patients with higher comorbidity scores had larger HA crystals. The present results suggest that the progressive increase in the hip fracture risk in elderly patients could be partially explained by the lower bone protein content in this age group.

Analysis of Related Factors of Brittle Hip Fracture in Postmenopausal Women with Osteoporosis.

OBJECTIVE: To investigate the effects of age, body mass index (BMI), bone mineral density (BMD), and levels of serum 25-hydroxyvitamin D (25OHD) on hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis. METHODS: A total of 252 postmenopausal women patients, whose bone density had reached the threshold of osteoporosis and age ≥50 years (50-98 years), collected from the Second Affiliated Hospital of Fujian Medical University from January 2015 to December 2018, were performed by retrospective analysis. According to whether or not they had a hip fracture, including femoral neck fracture or intertrochanteric fracture, the patients were divided into two groups, including 117 cases (50-84 years old) in the non-hip fracture group and 135 cases (57-98 years old) in the hip fracture group. BMD was measured by Hologic Discovery A DXA bone mineral densitometer. Levels of serum 25OHD were detected by ROCHE detection instrument. Comparisons of age, BMI, bone density of femoral neck, and levels of serum 25OHD between the two groups were performed by using the Student's t-test. Furthermore, the statistically significant factors were analyzed by multiple regression analysis to investigate the independent risk factors of hip fracture. RESULTS: The group without hip fracture: 117 cases; average age: 67.4 ± 8.5 years; BMI: 22.3 ± 3.2 kg/m2 ; bone density of femoral neck: (0.504 ± 0.067) g/cm2 ; T-value of femoral neck: -3.1 ± 0.6; levels of serum 25OHD: (24.9 ± 8.5) ng/mL. The group with brittle hip fracture: 135 cases; average age: 80.7 ± 7.6 years; BMI: 20.3 ± 3.5 kg/m2 ; bone density of femoral neck: (0.426 ± 0.077) g/cm2 ; T-value of femoral neck: -3.8 ± 0.7; levels of serum 25OHD: (15.9 ± 8.9) ng/mL. Age, BMI, bone density of femoral neck, and 25OHD level of the group without hip fracture were markedly lower than hip fracture group (P < 0.05). The results of logistic regression analysis suggested that age, bone density of femoral neck, and levels of serum 25OHD were independent risk factors for fragile hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis. CONCLUSION: Higher age, lower levels of bone density and 25OHD are the main risk factors of hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis.

Predicting bone strength from CT data: Clinical applications.

In this review we summarise over 15 years of research and development around the prediction of whole bones strength from Computed Tomography data, with particular reference to the prediction of the risk of hip fracture in osteoporotic patients. We briefly discuss the theoretical background, and then provide a summary of the laboratory and clinical validation of these modelling technologies. We then discuss the three current clinical applications: in clinical research, in clinical trials, and in clinical practice. On average the strength predicted with finite element models (QCT-FE) based on computed tomography is 7% more accurate that that predicted with areal bone mineral density from Dual X-ray Absorptiometry (DXA-aBMD), the current standard of care, both in term of laboratory validation on cadaver bones and in terms of stratification accuracy on clinical cohorts of fractured and non-fractured women. This improved accuracy makes QCT-FE superior to DXA-aBMD in clinical research and in clinical trials, where the its use can cut in half the number of patients to be enrolled to get the same statistical power. For routine clinical use to decide who to treat with antiresorptive drugs, QCT-FE is more accurate but less cost-effective than DXA-aBMD, at least when the decision is on first line treatment like bisphosphonates. But the ability to predict skeletal strength from medical imaging is now opening a number of other applications, for example in paediatrics and oncology.

Circulating amino acids are associated with bone mineral density decline and ten-year major osteoporotic fracture risk in older community-dwelling adults.

With aging, poor bone mineral density (BMD) and accelerated decrease in BMD are strong risk factors for fracture. Reports of the associations of dietary protein intake with bone strength are inconsistent, possibly owing to differences in protein sources and amino acid (AA) composition. We examined the associations of serum AA with 4-year hip BMD loss and subsequent fracture risk within 10 years in older community-dwelling adults, and further addressed whether lifestyle, dietary protein intake and its source, and body composition would affect the associations. In 1424 men and 1573 women (mean age 72 years), using binary logistic regression, higher serum valine, leucine, isoleucine and tryptophan concentrations were associated (or approaching a borderline significance in case of the last three ones) with less hip BMD decline (defined as BMD loss ≥ 2.8 times the precision error of the BMD measurement at femoral neck) in 4 years later, with the OR (95%CI) /SD of AA increase, ranging from 0.83 (0.75, 0.91) to 0.92 (0.87, 0.98) after multiple adjustments for baseline age, gender, BMI, BMD, estimated glomerular filtration rate (eGFR), dietary protein intake (animal- and plant-derived protein intakes), calcium intake, established lifestyles (physical activity level, smoking and alcohol drinking status), osteoporosis medications, and changes of body fat and lean muscle mass. Higher serum total homocysteine (tHcy) concentration was independently associated with BMD decline 4 years later (OR (95%CI) /SD of 1.16 (1.05, 1.27)). Using multivariate Cox regression, higher serum tryptophan concentration potentially predicted low risk of incident major osteoporotic fractures (MOFs) (HR/SD (95%CI)=0.86 (0.75, 0.98)) after multiple adjustments. Higher serum tHcy was associated with MOFs (HR/SD (95%CI)=1.29 (1.12, 1.50)) risk after multiple adjustments in men. These findings suggest that a specific AA profile correlates with greater BMD and lower subsequent fracture risk, independent of diet and lifestyle factors.

What is the importance of canal-to-diaphysis ratio on osteoporosis-related hip fractures?

OBJECTIVES: This study aims to investigate whether the ratio of the canal-to-diaphysis in femoral subtrochanteric region is helpful in determining risk before hip fracture. PATIENTS AND METHODS: The study group consisted of 116 patients with osteoporotic hip fractures (26 males, 90 females; mean age 77.8 years; range, 61 to 89 years) and the control group consisted of 56 subjects (11 males, 45 females; mean age 75.3 years; range, 60 to 83 years). The canal-to-diaphysis ratio of patients in the study group was measured on plain radiographs. The results of the affected side and intact side were compared. To ensure the interobserver reliability of the measurements and to minimize technical errors, the assessments were performed twice (two weeks apart) by two different orthopedic surgeons. RESULTS: The canal-to-diaphysis ratio was significantly increased in patients with hip fracture compared with the intact side of same patient (p<0.001) and control subjects (p<0.001). According to the results of the receiver operating characteristic analysis, canal-to-diaphysis ratio had a diagnostic value in predicting hip fracture in osteoporosis patients, and the limit value was approximately 0.53 (sensitivity: 81%, specificity: 86%). An index of 0.53 represents a risk of intertrochanteric hip fracture of 89%. CONCLUSION: This method can be easily applied by all physicians as X-ray device is readily accessible with low cost. The risk of hip fracture should be determined, osteoporosis should be evaluated, and treatment should be started in patients with high risk to take the necessary precautions before the fracture develops.

Maternal serum retinol, 25(OH)D and 1,25(OH)2D concentrations during pregnancy and peak bone mass and trabecular bone score in adult offspring at 26-year follow-up.

BACKGROUND: Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear. METHOD AND FINDINGS: Forty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986-88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) µmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 µmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS. CONCLUSIONS: This is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD.

Uso de bifosfonatos en pacientes con osteopenia / Biphosphonates in patients with osteopenia

La osteopenia, una disminución de la densidad mineral ósea de menor severidad que la osteoporosis, definida por valores de T-score entre -1,0 y -2,5 en la densitometría ósea , podría asociarse con un mayor riesgo de fracturas. Motivado por el pedido de una paciente con osteopenia que solicita a su médico algún medicamento que le ayude a disminuir su riesgo de fracturas, el autor se pregunta si los bifosfonatos podrían ser beneficiosos para las pacientes con este factor de riesgo. Luego de realizar una búsqueda bibliográfica y seleccionar la evidencia más reciente y de mejor calidad, se concluye que estos fármacos podrían ser útiles para prevenir fracturas en mujeres mayores de 65 años con elevado riesgo de fractura,independientemente del resultado de la densitometría. (AU)

Osteopenia, a minor decrease in bone mineral density, defined by T-score values between -1.0 and -2.5 in a bone densitometry, is associated with an increased risk of fractures. Moved by the request of a patient with osteopenia who asks her doctor for any medication that may help her reduce his risk of fractures, the author wonders if bisphosphonates could be beneficial for patients with this condition. After conducting a bibliographic search and selecting the most recent and best quality evidence, he concluded that these drugs could be useful to prevent fractures in women older than 65 years with ahigh risk of fracture, regardless of densitometry results. (AU)

Osteoporosis-related variations of trabecular bone properties of proximal human humeral heads at different scale lengths.

Osteoporosis (OP) is a skeletal disorder responsible for the weakening of the bone structure and, consequently, for an increased fracture risk in the elderly population. In the past, bone mineral density (BMD) variation was considered the best OP indicator, but recently the focus has shifted toward the variation of microstructural bone parameters. This work is based on the characterisation of 8-mm cylindrical biopsies harvested from proximal humeral heads belonging to healthy and osteoporotic patients, in order to assess the OP-related variations of bone properties at different scale lengths. In particular, bone biopsies underwent micro-computed tomography analysis to study the most relevant features of bone architecture and extrapolate the tissue mineral density (TMD) value of bone trabeculae. Compression tests and nanoindentations were performed to investigate the macro- and micromechanical properties of bone biopsies, respectively. In addition, XRD analyses were performed to obtain the mean hydroxyapatite (HA) crystallite size, while Raman spectroscopy investigated the collagen secondary structure. Thermogravimetric analysis was performed to evaluate the ratio between organic and inorganic phases. From the obtained results, OP samples showed a more anisotropic and less interconnected structure responsible for reduced compression strength. From this, it can be supposed that OP caused an alteration of bone structure that led to inferior macroscopic mechanical properties. Furthermore, OP samples possessed higher TMD and bigger HA crystals that are correlated to an increase of the hardness value obtained by means of nanoindentation. This less controlled HA crystal growth is probably due to an alteration of the organic matrix structure, as revealed by the increase of the random coil contribution in the Raman spectra of the OP bone. This higher crystal content led to an increase in trabecular density and hardness. In conclusion, the obtained data showed that OP affects bone properties at different scale lengths causing an alteration of its morphological, structural and mechanical features.