MTX Osteopathy Versus Osteoporosis Including Response to Treatment Data-A Retrospective Single Center Study Including 172 Patients.

MTX is an effective and widely used immunomodulatory drug for rheumatoid diseases. MTX osteopathy is a very rare and specific side effect, characterized by stress fractures at multiple locations in the lower extremity, hampering the patient's mobility by pain and loss of function. In clinical practice, osteoporosis and MTX osteopathy are repeatedly confused and a comparative workup is needed to clarity it's specifics. Furthermore, specific treatment options for MTX osteopathy need to be established. We compared patients suffering from MTX osteopathy to patients with osteoporosis (OPO). Patients underwent an extensive clinical workup including blood sampling, bone mineral density measurements, high-resolution peripheral quantitative computed tomography and muscular performance testing. Furthermore, treatment regimes in MTX osteopathy were compared with respect to regain of mobility and pain reduction. 83 patients with MTX osteopathy and 89 with OPO were included. Patients with MTX osteopathy did exhibit fractures predominantly at the lower extremity and pain scores were significantly higher (MTX: 6.75 ± 1.86 vs. OPO: 3.62 ± 2.95, p < 0.0001). MTX-caused mobility restriction was successfully reduced by treatment only if MTX was discontinued (pre-treatment: 2.16 ± 1.19 vs. post-treatment: 1.04 ± 0.87, p < 0.0001). Most mobility gain was achieved by involving anabolic treatment (anabolic: 2.1 ± 1.02 vs. antiresorptive: 1.09 ± 0.94, p < 0.05). In summary, MTX osteopathy is characterized by distinct lower extremity stress fractures leading to severe pain and immobility. Discontinuation of MTX is essential to enable treatment success and involving anabolic treatment seems to be more effectively in mobility regain as antiresorptive treatment alone.

Sex-Specific Association Patterns of Bone Microstructure and Lower Leg Arterial Calcification.

In conversations about bone loss and the importance of calcium homeostasis, patients frequently inquire about the association with arterial calcifications. Although a relationship between bone loss and the occurrence of vascular calcifications is suspected, it is not yet fully investigated and understood. This study aims to analyze associations between bone mineralization, structure, and vascular calcification at the lower leg in patients with low bone mineral density in HR-pQCT. We retrospectively analyzed 774 high-resolution quantitative computed tomography (HR-pQCT) scans of the distal tibia for the presence of vascular calcifications. After sex-specific propensity score matching for age and BMI to account for confounders, 132 patients remained for quantification of bone microstructure, bone density, lower leg arterial calcification (LLAC), and laboratory parameters of bone turnover. The interactions between bone parameters and vascular calcification were quantified by regression analyses. The calcium metabolism was not different between individuals with and without LLAC, nor oral calcium supplementation. Female patients with LLAC had a higher cortical perimeter (p = 0.016) compared to female patients without LLAC, whereas male patients with LLAC had lower cortical pore diameter than male patients without LLAC (p = 0.027). The appearance of LLAC was sex specifically associated with bone parameters. In female patients, only plaque density was associated with HR-pQCT bone parameters and age, whereas in male patients, plaque volume was associated with HR-pQCT parameters of the distal tibia. Female patients exhibit an increasing plaque density depended on age and trabecular thinning. Decreasing cortical pore diameter and trabecular number along with increasing bone mineralization are linked to increasing plaque volume in male patients.

TBS correlates with bone density and microstructure at trabecular and cortical bone evaluated by HR-pQCT.

INTRODUCTION: Trabecular bone score (TBS) estimates bone microstructure, which is directly measured by high-resolution peripheral quantitative computed tomography (HRpQCT). We evaluated the correlation between these methods and TBS influence on fracture risk assessed by FRAX. MATERIALS AND METHODS: We evaluated 129 individuals (82 women, 43 postmenopausal) 20 to 82.3 years without prevalent clinical or non-clinical morphometric vertebral fractures, using DXA (spine and hip), HR-pQCT at distal radius (R) and tibia (T) and TBS which classifies bone microarchitecture as normal (TBS ≥ 1.350), partially degraded (1.200 < TBS < 1.350), or degraded (TBS ≤ 1.200). RESULTS: Spine and hip BMD and HR-pQCT parameters at cortical bone: area (T), density (R,T) thickness (T) and trabecular bone: density (R,T), number (T) and thickness (R) were significantly better in the 78 individuals with normal TBS (group 1) versus the 51 classified as partially degraded (n = 42) or degraded microarchitecture (n = 9) altogether (group 2). TBS values correlated with age (r = - 0.55), positively with spine and hip BMD and all cortical and trabecular bone density and microstructure parameters evaluated, p < 0.05 all tests. Binary logistic regression defined age (p = 0.008) and cortical thickness (p = 0.018) as main influences on TBS, while ANCOVA demonstrated that HR-pQCT data corrected for age were not different between TBS groups 1 and 2. TBS adjustment increased FRAX risk for major osteoporotic fractures and hip fractures. CONCLUSION: We describe significant association between TBS and both trabecular and cortical bone parameters measured by HR-pQCT, consistent with TBS influence on fracture risk estimation by FRAX, including hip fractures, where cortical bone predominates.

Changes in bone density and microarchitecture in adolescents undergoing a first kidney transplantation: a prospective study.

PURPOSE: Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx), being due to pre-existing CKD-MBD, immunosuppressive therapies, and post-KTx hypophosphatemia. This study aimed to evaluate bone biomarkers and microarchitecture using high resolution peripheral quantitative computed tomography (HR-pQCT) at the time of KTx and 6 months thereafter and to compare these results with those of matched healthy controls (HC). METHODS: This study presented the single-center subgroup of patients aged between 10 and 18 years included in the prospective "Bone Microarchitecture in the Transplant Patient" study (TRANSOS-NCT02729142). Patients undergoing a first KTx were matched (1:2) with HC from the "Vitamin D, Bones, Nutritional and Cardiovascular Status" cohort (VITADOS) on sex, pubertal stage, and age. RESULTS: At a median (interquartile range, IQR) age of 15 [13; 16] years, 19 patients (6 girls, 7 pre-emptive KTx, 7 steroid-sparing immunosuppressive strategies) underwent a first KTx, with a median [IQR] parathyroid hormone level of 1.9 [1.4; 2.9] the upper limit of normal (ULN). Higher total and trabecular bone densities, along with superior trabecular microarchitecture, were observed at KTx compared to HC. Six months post-KTx, patients had significantly impaired trabecular parameters at the radius, while results were not significantly different at the weight-bearing tibia, neither cortical parameters at both sites. Six months post-KTx, 6 (32%) patients still present with metabolic acidosis, 10 (53%) persistent hyperparathyroidism (always < 2 ULN), and 5 (26%) elevated FGF23 levels; 11 (58%) received phosphate supplementation. CONCLUSIONS: Bone density and microarchitecture at the time of KTx were superior compared to HC, but radial trabecular bone microarchitecture impairment observed 6 months post-KTx may reflect subtle albeit present post-KTx CKD-MBD. What is Known? • Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx) and is associated with morbidity. However, biochemical parameters and dual X-ray absorptiometry (DXA) are poor predictors of the underlying bone disease. What is new? • The present study on 19 adolescent KTx recipients with adequate CKD-MBD control at the time of KTx reveals no significant bone disease compared to matched healthy controls. Microarchitecture impairment observes 6 months post-KTx may reflect subtle, albeit present, post-KTx CKD-MBD.

Micronutrient Status During Military Training and Associations With Musculoskeletal Health, Injury, and Readiness Outcomes.

OBJECTIVE: Micronutrient status, specifically vitamin D and iron, represent modifiable factors for optimizing military readiness. The primary purpose of this investigation was to determine associations between micronutrient deficiency (i.e., iron status and 25-hydroxy-vitamin D [25(OH)D]) and operationally relevant outcomes (i.e., skeletal health, musculoskeletal injury) at baseline and post-10 weeks of arduous military training. METHODS: A total of 227 (177 men, 50 women) Marine Officer Candidates School (OCS) candidates who completed OCS training with complete data sets were included in this analysis. Vitamin D and iron status indicators were collected at two timepoints, pre (baseline) and post OCS. Musculoskeletal outcomes at the mid- and proximal tibial diaphysis were assessed via peripheral quantitative computed tomography. RESULTS: Micronutrient status declined following OCS training in men and women and was associated with musculoskeletal outcomes including greater bone strength (strength strain index) at the mid-diaphysis site in those with optimal status (M = 38.26 mm3, SE = 15.59) versus those without (M = -8.03 mm3, SE = 17.27). In women (p = .037), endosteal circumference was greater in the deficient group (M = 53.26 mm, SE = 1.19) compared with the optimal group (M = 49.47 mm, SE = 1.31) at the proximal diaphysis. In men, greater baseline hepcidin concentrations were associated with an increased likelihood of suffering musculoskeletal injury during training. CONCLUSIONS: Vitamin D and iron status declined over the course of training, suggesting impaired micronutrient status. Differences in musculoskeletal outcomes by micronutrient group suggests optimal vitamin D and ferritin concentrations may exert beneficial effects on bone fatigability and fracture reduction during military training.

Comparison of bone microstructure and strength in the distal radius and tibia between the different types of primary hypertrophic osteoarthropathy: an HR-pQCT study.

Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients. PURPOSE: The primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients. METHODS: Twenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated. RESULTS: Compared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength. CONCLUSION: PHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients.

Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa.

Between-scanner differences in measures of bone and body composition can obscure or exaggerate physiological differences in multi-site studies or the magnitude of changes in longitudinal studies. We conducted a cross-calibration study at two bone imaging centres in The Gambia, West Africa where DXA (dual-energy X-ray absorptiometry) and pQCT (peripheral Quantitative-Computed Tomography) are routinely used. Repeat scans were obtained from 64 Gambian adults (58% Male) aged Mean(SD) 30.9 (13.5) years with Mean(SD) body mass index (BMI) 21.7 (4.0) kg/m2, using DXA (GE Lunar iDXA, whole body [WB], total hip [TH], lumbar spine [LS]) and pQCT (Stratec XCT2000L/XCT2000, tibia 4%, 50% sites). Between-scanner differences were tested using paired t tests (p < 0.05). Between-scanner correlation was explored with linear regression, and cross-calibration equations derived. Bland-Altman analysis investigated machine trend/bias. When differences were detected (p < 0.05), cross-calibration equations were applied to urban values, with t tests and Bland Altman analysis repeated. Between-scanner differences exceeded the predefined level of statistical significance (p < 0.05) for WB aBMD and BA; all pQCT measures vBMD, BMC, cortical cross-sectional area (CSA) and stress-strain index (SSI). Between-scanner correlation was high (R2:0.92-0.99), except pQCT Mu.Den (R2 = 0.51). Bland Altman plots indicated bias increased with increasing BMD. Cross-calibration equations attenuated all between-scanner differences and systematic bias. Cross-calibration, particularly of pQCT scanners, is an important consideration in multi-site studies particularly where between population comparisons are intended. Our experiences and findings may be generalisable to other resource-limited settings where the logistics of sourcing parts and in-country repair may result in lengthy scanner downtime.

Analysis of Three-Dimensional Bone Microarchitecture of the Axis Exposes Pronounced Regional Heterogeneity Associated with Clinical Fracture Patterns.

The odontoid process (dens) of the second cervical vertebra (axis) is prone to fracture. While the importance of its skeletal integrity has been previously noted, representative three-dimensional microarchitecture analyses in humans are not available. This study aimed to determine the bone microarchitecture of the axis using high-resolution quantitative computed tomography (HR-pQCT) and to derive clinical implications for the occurrence and treatment of axis fractures. For initial clinical reference, the apparent density of the axis was determined based on clinical computed tomography (CT) images in patients without and with fractures of the axis. Subsequently, 28 human axes (female 50%) obtained at autopsy were analyzed by HR-pQCT. Analyses were performed in three different regions corresponding to zones I (tip of dens), II (base of dens), and III (corpus axis) of the Anderson and D'Alonzo classification. Lower apparent densities based on clinical CT data were detected in zone II and III compared to zone I in both the group without and with fracture. In the autopsy specimens, cortical thickness and bone volume fraction decreased continuously from zone I to zone III. Trabecular and cortical tissue mineral density was lowest in zone III, with no differences between zones I and II. In conclusion, our clinical and high-resolution ex vivo imaging data highlight a marked regional heterogeneity of bone microarchitecture, with poor cortical and trabecular properties near the dens base. These results may partly explain why zones II and III are at high risk of fracture and osteosynthesis failure.

Assessment of Bone Microarchitecture in Patients with Systemic Mastocytosis and its Association with Clinical and Biochemical Parameters of the Disease.

Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (ρ, 0.46; P = 0.036) and tibia (ρ, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (ρ, -0.46; P = 0.035) and tibia (ρ, -0.52; P = 0.016). Strong and positive associations between F.load (ρ, 0.75; P < 0.001) and stiffness (ρ, 0.70; P < 0.001) at the radius, and between F.load at the tibia (ρ, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength.

Evaluation of Volumetric Bone Mineral Density, Bone Microarchitecture, and Bone Strength in Patients with Achondroplasia Caused by FGFR3 c.1138G > A Mutation.

Achondroplasia (ACH) is a skeletal disorder caused by fibroblast growth factor receptor 3 (FGFR3) variants. Volumetric bone mineral density (vBMD), bone microarchitecture, and strength have not been evaluated in these patients previously. This study aims to evaluate vBMD, bone microarchitecture, and strength in ACH patients. Seventeen patients underwent clinical and biochemical evaluations, and genetic testing. High-resolution peripheral quantitative computed tomography was performed in 10 ACH patients and 21 age- and sex-matched healthy subjects. All individuals had the hotspot mutation of c.1138G > A in FGFR3. Linear growth retardation, disproportionate short stature, and genu varum are the most common manifestations. The mean height was 108.82 ± 24.08 cm (Z score: - 5.72 ± 0.96). Total vBMD in the ACH and the control groups was 427.08 ± 49.29 mg HA/cm3 versus 300.35 ± 69.92 mg HA/cm3 (p < 0.001) at the radius and 336.90 ± 79.33 mg HA/cm3 versus 292.20 ± 62.35 mg HA/cm3 (p = 0.098) at the tibia; both at the radius and tibia, vBMD of trabecular bones was significantly lower in the ACH group than in the control group, but vBMD of cortical bones was slightly higher in the ACH group. Trabecular separation and cortical thickness in the ACH group were significantly higher than those in the control group, but trabecular number was significantly decreased in the ACH group. Stiffness and failure load were only better at the radius in the ACH group. ACH patients have higher total and cortical vBMD, lower trabecular vBMD, worse trabecular bone microarchitecture, thicker cortical bone thickness, and better estimated bone strength.

Radial HR-pQCT and Finite Element Analysis in HPP Patients are Superior in Identifying Susceptibility to Fracture-Associated Skeletal Affections Compared to DXA and Laboratory Tests.

Hypophosphatasia (HPP) is an inborn disease that causes a rare form of osteomalacia, a mineralization disorder affecting mineralized tissues. Identification of patients at high risk for fractures or other skeletal manifestations (such as insufficiency fractures or excessive bone marrow edema) by bone densitometry and laboratory tests remains clinically challenging. Therefore, we examined two cohorts of patients with variants in the ALPL gene grouped by bone manifestations. These groups were compared by means of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) and simulated mechanical performance utilizing finite element analysis (FEA). Whereas the incidence of skeletal manifestations among the patients could not be determined by dual energy X-ray absorptiometry (DXA) or laboratory assessment, HR-pQCT evaluation showed a distinct pattern of HPP patients with such manifestations. Specifically, these patients had a pronounced loss of trabecular bone mineral density, increased trabecular spacing, and decreased ultimate force at the distal radius. Interestingly, the derived results indicate that the non-weight-bearing radius is superior to the weight-bearing tibia in identifying deteriorated skeletal patterns. Overall, the assessment by HR-pQCT appears to be of high clinical relevance due to the improved identification of HPP patients with an increased risk for fractures or other skeletal manifestations, especially at the distal radius.

Bone density, microarchitecture and estimated strength in stone formers: a cross-sectional HR-pQCT study.

BACKGROUND: Low areal bone mineral density (BMD), increased fracture risk and altered bone remodeling have been described among stone formers (SFs), but the magnitude of these findings differs by age, sex, menopausal status and urinary calcium (uCa). This study aimed to investigate volumetric BMD (vBMD), bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SFs, irrespective of calciuria, further distinguishing trabecular from cortical compartments. METHODS: HR-pQCT/FEA was performed at the distal tibia (DT) and distal radius (DR) in 106 SFs (57 males and 49 premenopausal females; median age 37 years) and compared with 106 non-SFs (NSFs) retrieved from an existing database, matched for age, sex and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SFs. RESULTS: SFs exhibited significantly lower trabecular number (TbN) and higher trabecular separation (TbSp) than NSFs at both anatomical sites and lower cortical porosity in the DR. In a subgroup analysis separated by sex, female SFs presented significantly lower TbvBMD, relative bone volume fraction (BV/TV) and TbN and higher TbSp than NSFs at both sites, while male SFs showed significantly lower stiffness and failure load. Multivariate analysis showed TbN to be independently associated with sex and BMI at both sites and with uCa at the DR. CONCLUSIONS: The present findings suggest that bone disease represents an early event among SFs, associated at least in part with calcium excretion and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.

Bone-specific physical activity questionnaire-derived skeletal loading score predicts bone geometry, density, and strength indices: a cross-sectional study.

INTRODUCTION: The bone-specific physical activity questionnaire (BPAQ) provides a bone-relevant index of physical activity participation according to the mechanical loads experienced across the life span. MATERIALS AND METHODS: We aimed to examine relationships between historical bone-relevant physical activity and pQCT-derived parameters of bone strength. We recruited 532 healthy volunteers (277 males, 255 females) across a broad age range (4-97 years). Peripheral quantitative computed tomography (XCT-3000, Stratec, Germany) was used to examine volumetric bone density, area, and strength indices of the non-dominant tibia and radius. Exercise loading history from birth was determined using the past BPAQ (pBPAQ) score. Pearson correlation analysis was used to examine relationships between pBPAQ scores and pQCT parameters. RESULTS: Independent of sex, pBPAQ scores were associated with total density at the 38% and 66% tibial sites and the 66% radial site (r = 0.145-0.261, p ˂ 0.05), total area at the 38% tibial site and 4% and 66% radial sites (r = 0.129-0.156, p ˂ 0.05), and strength indices at all measured sites (r = 0.123-0.234, p < 0.05). CONCLUSION: We conclude that, independent of sex, historical bone-relevant physical activity is associated with pQCT-derived indices of bone strength, indicating that pBPAQ captures the characteristics of bone loading history that are likely to be relevant adaptive stimuli. A larger sample is required to examine the influence of age on this relationship.

Denosumab improves bone mineral density and microarchitecture in rheumatoid arthritis: randomized controlled trial by HR-pQCT.

INTRODUCTION: This pre-specified exploratory analysis investigated the effect of denosumab on bone mineral density (BMD) and bone microarchitecture in patients with rheumatoid arthritis (RA) treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). MATERIALS AND METHODS: In this open-label, parallel-group study, patients were randomly assigned (1:1) to continuous treatment with csDMARDs plus denosumab or continuous treatment with csDMARD therapy alone for 12 months. BMD and bone microarchitecture were measured by dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Of 46 patients enrolled in the primary study, 43 were included in the full analysis set. The mean age was 65.3 years, 88.4% were female, and 60.5% had osteoporosis. Areal BMD of the lumbar spine increased from baseline to 6 and 12 months in both groups, but the increase was higher in the csDMARDs plus denosumab group. Areal BMD of the total hip and femoral neck increased from baseline to 6 and 12 months only in the csDMARDs plus denosumab group. Cortical volumetric BMD and cortical thickness of the distal tibia increased in the csDMARDs plus denosumab group at 6 and 12 months but decreased in the csDMARD therapy alone group. Trabecular bone parameters of the distal tibia improved only in the csDMARDs plus denosumab group at 12 months. CONCLUSION: Denosumab may be recommended for patients with RA treated with csDMARDs to increase BMD and improve bone microarchitecture.

Recommendations for High-resolution Peripheral Quantitative Computed Tomography Assessment of Bone Density, Microarchitecture, and Strength in Pediatric Populations.

PURPOSE OF REVIEW: The purpose of this review is to summarize current approaches and provide recommendations for imaging bone in pediatric populations using high-resolution peripheral quantitative computed tomography (HR-pQCT). RECENT FINDINGS: Imaging the growing skeleton is challenging and HR-pQCT protocols are not standardized across centers. Adopting a single-imaging protocol for all studies is unrealistic; thus, we present three established protocols for HR-pQCT imaging in children and adolescents and share advantages and disadvantages of each. Limiting protocol variation will enhance the uniformity of results and increase our ability to compare study results between different research groups. We outline special cases along with tips and tricks for acquiring and processing scans to minimize motion artifacts and account for growing bone. The recommendations in this review are intended to help researchers perform HR-pQCT imaging in pediatric populations and extend our collective knowledge of bone structure, architecture, and strength during the growing years.

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

Precision errors and least significant changes in paediatric forearm measurements of bone density, mass, dimensions, mechanostat parameters and soft tissue composition by Stratec XCT-2000L.

OBJECTIVES: The peripheral quantitative computed tomography (pQCT) is gaining popularity in the field of paediatric densitometry, however, very little is known about the precision errors of this method in diseased children. The aim of the study was to evaluate the precision errors of bone density, mass, dimensions, strength, mechanostat parameters and soft tissue at the forearm in diseased children. METHODS: Stratec XCT 2000L apparatus was used. The measurement sites were 4% and 66% of the forearm length. The study group consisted of 60 patients (31 girls) aged 5,7-18,0 yrs. RESULTS: We observed week relationships between precision errors and body size with r from -0,37 to 0,28. Relative precision errors (CV%RMS) were from 0,85% for radius 66% cortical bone density to 3,82% for fat cross-sectional area to muscle cross-sectional area ratio. Least significant change (LSC) was from 2,73% to 10,59%, respectively. CONCLUSION: Presented study reveal pQCT method at the forearm in diseased children as relatively precise technique. The results may help with planning and interpretation of pQCT studies in diseased children.

Non-traditional HIIT-style ROTC training elicits positive bone quality and performance adaptations.

Military personnel experience elevated bone injury incidence, partly due to arduous and repetitive training. Non-traditional High-Intensity Interval Training-style (HIIT) may benefit pre-enlisted Reserve Officer Training Corps (ROTC) cadet's musculoskeletal health and performance prior to military service. This study investigated 16 ROTC (n = 12 males; n = 4 females) and 15 physically active sex-, age-, and body mass-matched Controls' musculoskeletal health and performance from November to April. Total body, lumbar spine, and dual- hip dual-energy X-ray absorptiometry scans and 4%, 38%, 66% tibial peripheral quantitative computed tomography scans, blood draws (serum sclerostin and parathyroid hormone), and maximal muscle strength and aerobic capacity testing were completed. From November to April, ROTC improved bone density (DXA) of the dominant total hip and greater trochanter and non-dominant greater trochanter and 38% and 66% tibial total volumetric and cortical bone density (pQCT) similarly or more than Controls (all p ≤ 0.049). From November to April, ROTC also improved bench and leg press, and peak aerobic capacity (all p ≤ 0.013). From November to January, serum sclerostin increased (p ≤ 0.007) and remained elevated through April, while parathyroid hormone was unchanged. HIIT-style training induced positive musculoskeletal adaptations, suggesting it may be an excellent pre-service training modality for this injury prone group.

Diagnostic accuracy of high-resolution peripheral quantitative computed tomography and X-ray for classifying erosive rheumatoid arthritis.

OBJECTIVE: To investigate whether high-resolution peripheral quantitative CT (HR-pQCT) of two metacarpophalangeal (MCP) joints can more accurately classify patients as having erosive RA compared with conventional radiography (CR) of 44 joints in the hands, wrists and feet. METHODS: In this single-centre cross-sectional study, patients with established RA (disease duration ≥5 years) were investigated by HR-pQCT and CR. The second and third MCP joints of the dominant hand were assessed for erosions by HR-pQCT. CR of the hands, wrists and feet were scored according to the Sharp-van der Heijde (SHS) method. RESULTS: In total, 353 patients were included; 66 (18.7%) patients were classified as having non-erosive RA, and 287 (81.3%) had erosive RA by CR. The sensitivity and specificity (95% CI) of HR-pQCT for classifying patients as having erosive RA when standard CR of hands, wrists and feet was used as the reference was 89% (84, 92%) and 30% (20, 43%), respectively. Using HR-pQCT as the reference, the sensitivity and specificity of CR for classifying patients having erosive RA were 85% (80, 89%) and 38% (25, 52%), respectively. McNemar's χ2 test showed no significant difference between the sensitivities of patients classified as having erosive RA by HR-pQCT or by CR (2.14, P = 0.177). CONCLUSION: The diagnostic accuracy of HR-pQCT scanning of only two MCP joints and CR of 44 joints suggests the two modalities were comparable for classifying patients with established RA as having erosive disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03429426).

Hind limb muscles influence the architectural properties of long bones in frogs.

The Mechanostat Theory states that osteocytes sense both the intensity and directionality of the strains induced by mechanical usage and modulate the bone design accordingly. In long bones, this process may adapt anterior-posterior and lateral-medial strength to their mechanical environment showing regional specificity. Anuran species are ideal for analyzing the muscle-bone relationships related to the different mechanical stresses induced by their many locomotor modes and habitat uses. This work aimed to explore the relationships between indicators of the force of the most relevant muscles to locomotion and the mechanical properties of femur and tibia fibula in preserved samples of three anuran species with different habitat use (aquatic, arboreal) and locomotion modes (swimmer, jumper, walker/climber). For that purpose, we measured the anatomical cross-sectional area of each dissected muscle and correlated it with the moments of inertia and bone strength indices. Significant, species-specific covariations between muscle and bone parameters were observed. Pseudis platensis, the aquatic swimmer, showed the largest muscles, followed by Boana faber, the jumper and Phyllomedusa sauvagii, the walker/climber. As we expected, bigger muscles correlate with bone parameters in all the species. Nevertheless, smaller muscles also play an important role in bone design. In aquatic species, muscle interaction enhances mostly lateral bending strength throughout the femur and lateral and antero-posterior bending strength in the tibia fibula. In the jumper species, muscles affected the femur and tibia fibula mostly in anterior-posterior bending. In the walker/climber species, responses involving both antero-posterior and lateral bending strengths were observed in the femur and tibia fibula. These results show that bones will be more or less resistant to lateral and antero-posterior bending according to the different mechanical challenges of locomotion in aquatic vs. arboreal habitats. This study provides new evidence of the muscle-bone relationships in three frog species associated with their different locomotion and habitat uses, highlighting the crucial role of muscle in determining the architectural properties of bones.