Trabecular bone score in adults with type 1 diabetes: a meta-analysis.

Type 1 diabetes mellitus (T1DM) is associated with a disproportionately high fracture rate despite a minimal decrease in bone mineral density. Though trabecular bone score (TBS), an indirect measure of bone architecture, is lower in adults with T1DM, the modest difference is unlikely to account for the large excess risk and calls for further exploration. INTRODUCTION: Fracture rates in type 1 diabetes mellitus (T1DM) are disproportionately high compared to the modestly low bone mineral density (BMD). Distortion of bone microarchitecture compromises bone quality in T1DM and is indirectly measured by trabecular bone score (TBS). TBS could potentially be used as a screening tool for skeletal assessment; however, there are inconsistencies in the studies evaluating TBS in T1DM. We performed this meta-analysis to address this knowledge gap. METHODS: An electronic literature search was conducted using PubMed, Scopus, and Web of Science resources (all-year time span) to identify studies relating to TBS in T1DM. Cross-sectional and retrospective studies in adults with T1DM were included. TBS and BMD data were extracted for pooled analysis. Fracture risk could not be analyzed as there were insufficient studies reporting it. RESULT: Data from six studies were included (T1DM: n = 378 and controls: n = 286). Pooled analysis showed a significantly lower TBS [standardized mean difference (SMD) = - 0.37, 95% CI - 0.52 to - 0.21; p < 0.00001] in T1DM compared to controls. There was no difference in the lumbar spine BMD (6 studies, SMD - 0.06, 95% CI - 0.22 to 0.09; p = 0.43) and total hip BMD (6 studies, SMD - 0.17, 95% CI - 0.35 to 0.01; p = 0.06) in the case and control groups. CONCLUSIONS: Adults with T1DM have a lower TBS but similar total hip and lumbar spine BMD compared to controls. The risk attributable to the significant but limited difference in TBS falls short of explaining the large excess propensity to fragility fracture in adults with T1DM. Further studies on clarification of the mechanism and whether TBS is suited to screen for fracture risk in adults with T1DM are necessary.

The relationship between bone strain index, bone mass, microarchitecture and mechanical behavior in human vertebrae: an ex vivo study.

The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice. PURPOSE: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae. METHODS: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness. RESULTS: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06). CONCLUSION: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD.

Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Deficits in volumetric bone mineral density, bone microarchitecture, and estimated bone strength in women with atypical anorexia nervosa compared to healthy controls.

OBJECTIVE: Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. METHOD: Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21-46 years. RESULTS: Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p < .05). Adjusting for weight, deficits in tibial cortical bone variables persisted (p < .05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high-resolution peripheral quantitative computed tomography (HR-pQCT) variables in atypical anorexia nervosa. DISCUSSION: Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR-pQCT variables are associated with increased fracture risk. PUBLIC SIGNIFICANCE: Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation.

Quality of life in postmenopausal women with osteoporosis and osteopenia: associations with bone microarchitecture and nutritional status.

PURPOSE: Primary aim of the study was to investigate the status of different health-related quality of life (HRQoL) domains in postmenopausal women with osteoporosis and osteopenia, and to explore possible associations with bone microarchitecture and nutritional status. METHODS: This was a single-center cross-sectional study that included 232 postmenopausal women, from which they were divided into three groups-osteoporosis (OP, N = 63), osteopenia (OPIA, N = 123), and control group (N = 46). Detailed medical history data and anthropometric measurements were taken from all women. Bone structure parameters were taken with DXA device, with additional analysis of bone microarchitecture status with Trabecular Bone Score (TBS). Nutritional status was assessed with Mini Nutritional Assessment (MNA) questionnaire, and HRQoL with Medical Outcomes Study Short Form-36 (SF-36) questionnaire. RESULTS: Nutrition evaluation analysis have shown that patients in OP group had significantly lower values of MNA score compared to the OPIA group and control group (P = 0.005). Furthermore, a significant positive correlation was found between all of the SF-36 domains and MNA scores, while significant positive correlation was found between TBS values and Physical functioning (P < 0.001), Bodily pain (P = 0.027), Social functioning (P = 0.029), and Vitality domains (P = 0.041) in total investigated population. Further analyses were performed only in OP and OPIA groups, and TBS score showed significant positive correlation with Physical functioning (r = 0.248, P < 0.001) and Bodily pain domains as well (r = 0.180, P = 0.014), while MNA score positively correlated with each of the SF-36 domains. Multiple regression models have shown that MNA score retained significant association with each SF-36 domains, and TBS value with Physical functioning (P = 0.003), Social functioning (P = 0.012), and Vitality domains (P = 0.014). CONCLUSION: This study highlights the associations that TBS has with some domains of HRQoL in postmenopausal women with osteoporosis and osteopenia. Moreover, nutritional status could play a role in the complex interplay between TBS and HRQoL.

Photon-Counting Computed Tomography for Microstructural Imaging of Bone and Joints.

PURPOSE OF REVIEW: Recently, photon-counting computed tomography (PCCT) has been introduced in clinical research and diagnostics. This review describes the technological advances and provides an overview of recent applications with a focus on imaging of bone. RECENT FINDINGS: PCCT is a full-body scanner with short scanning times that provides better spatial and spectral resolution than conventional energy-integrating-detector CT (EID-CT), along with an up to 50% reduced radiation dose. It can be used to quantify bone mineral density, to perform bone microstructural analyses and to assess cartilage quality with adequate precision and accuracy. Using a virtual monoenergetic image reconstruction, metal artefacts can be greatly reduced when imaging bone-implant interfaces. Current PCCT systems do not allow spectral imaging in ultra-high-resolution (UHR) mode. Given its improved resolution, reduced noise and spectral imaging capabilities PCCT has diagnostic capacities in both qualitative and quantitative imaging that outperform those of conventional CT. Clinical use in monitoring bone health has already been demonstrated. The full potential of PCCT systems will be unlocked when UHR spectral imaging becomes available.

Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma.

PURPOSE: Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL). METHODS: A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and ß-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. RESULTS: PPGL patients had a higher level of ß-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent. CONCLUSIONS: PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Impact of pheochromocytoma or paraganglioma on bone metabolism: A systemic review and meta-analysis.

INTRODUCTION: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap. METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP). RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery. CONCLUSION: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

Changes of the subchondral bone microchannel network in early osteoarthritis.

OBJECTIVE: We have identified a 3D network of subchondral microchannels that connects the deep zone of cartilage to the bone marrow (i.e., cartilage-bone marrow microchannel connectors; CMMC). However, the pathological significance of CMMC is largely unknown. Here, we quantitatively evaluated how the CMMC microarchitecture is related to cartilage condition, as well as regional differences in early idiopathic osteoarthritis (OA). METHODS: Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified, and a biopsy-based high-resolution micro-CT imaging was employed. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and the CMMC morphology were quantified and compared between the two groups. The effect of joint's region and cartilage condition was examined on each dependent variable. RESULTS: The CMMC number and morphology were affected by region of the joint, but not by cartilage condition. On the other hand, the minimum and maximum CMMC size was changed by both the location on the joint, as well as the cartilage condition. The smallest CMMC were consistently detected at the load-bearing region (LBR) of the joint. Compared to non-pathological subjects, the size of the microchannels was enlarged in early OA, most noticeably at the non-load-bearing region (NLBR) and the peripheral rim (PR) of the femoral head. Furthermore, subchondral bone thinning was observed in early OA as a localized occurrence linked with areas of partial chondral defect. CONCLUSION: Our data point to an enlargement of the SB microchannel network, and a collective structural deterioration of SB in early idiopathic OA.

Trabecular bone score and bone mineral density as indices of skeletal fragility in endogenous Cushing's syndrome.

OBJECTIVE: Endogenous Cushing's syndrome (CS) is a known cause of secondary osteoporosis. Vertebral fractures (VFs) in endogenous CS may occur despite normal bone mineral density (BMD). Trabecular bone score (TBS) is a relatively new, non-invasive technique to assess bone microarchitecture. The objective of our study was to analyse the BMD and bone microarchitecture using TBS in endogenous CS and compare it with a group of age and sex-matched healthy controls, and also analyse the factors predicting BMD and TBS. DESIGN: Cross-sectional study of cases and controls. PATIENTS AND MEASUREMENTS: We included 40 female patients with overt endogenous CS, out of which 32 were adrenocorticotropic hormone (ACTH)-dependent CS and 8 were ACTH-independent. We also included 40 healthy, female controls. Both patients and controls were subjected to an assessment of biochemical parameters and BMD and TBS. RESULTS: Patients with endogenous CS had significantly lower BMD at the lumbar spine, femoral neck, and total hip and significantly lower TBS than healthy controls (all p < .001), while no significant difference was noted in the distal radius BMD (p = .055). In endogenous CS, a large proportion of patients, n = 13 (32.5%) had normal BMD for age (BMD Z-score ≥ -2.0) with low TBS (L1 -L4 TBS ≤ 1.34). TBS correlated negatively with HbA1c (p = .006), and positively with serum T4 (p = .027). CONCLUSION: TBS should be considered an important complementary tool in addition to BMD for the routine assessment of skeletal health in CS.

C-reactive protein predicts endocortical expansion but not fracture in older men: the prospective STRAMBO study.

In older men, higher high-sensitivity C-reactive protein (hsCRP) concentrations were associated with faster prospectively assessed endocortical expansion (distal radius, distal tibia) and slightly higher cortical bone loss at distal tibia, but not with the fracture risk. High hsCRP level has a limited impact on bone decline in older men. PURPOSE: Data on the link of the high-sensitivity C-reactive protein (hsCRP) with bone loss and fracture risk are discordant. We studied the association of the hsCRP with the prospectively assessed decrease in areal bone mineral density (aBMD), bone microarchitecture decline, and fracture risk in older men. METHODS: At baseline, hsCRP was measured in 823 men aged 60-88. Areal BMD and bone microarchitecture (distal radius, distal tibia) were assessed by dual-energy X-ray absorptiometry and high-resolution peripheral QCT, respectively, at baseline and after 4 and 8 years. Data on incident fractures were collected for 8 years. RESULTS: Higher hsCRP concentration was associated with faster increase in aBMD at the whole body and lumbar spine, but not other sites. Higher hsCRP levels were associated with faster decrease in cortical area and more rapid increase in trabecular area at the distal radius (0.048 mm2/year/SD, p < 0.05) and distal tibia (0.123 mm2/year/SD, p < 0.001). At the distal tibia, high hsCRP level was associated with greater decrease in total and cortical volumetric BMD (vBMD) and in failure load. The hsCRP levels were not associated with the fracture risk, even after accounting for competing risk of death. CONCLUSION: Higher hsCRP levels were associated with greater endocortical expansion at the distal radius and tibia. Higher hsCRP was associated with slightly faster decrease in total and cortical vBMD and failure load at distal tibia, but not with the fracture risk. Thus, high hsCRP levels are associated with faster cortical bone loss, but not with fracture risk in older men.

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.

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

Bone Microarchitecture and Volumetric Mineral Density Assessed by HR-pQCT in Patients with 21- and 17α-Hydroxylase Deficiency.

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.

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.

Characterizing Bone Phenotypes Related to Skeletal Fragility Using Advanced Medical Imaging.

PURPOSE OF REVIEW: Summarize the recent literature that investigates how advanced medical imaging has contributed to our understanding of skeletal phenotypes and fracture risk across the lifespan. RECENT FINDINGS: Characterization of bone phenotypes on the macro-scale using advanced imaging has shown that while wide bones are generally stronger than narrow bones, they may be more susceptible to age-related declines in bone strength. On the micro-scale, HR-pQCT has been used to identify bone microarchitecture phenotypes that improve stratification of fracture risk based on phenotype-specific risk factors. Adolescence is a key phase for bone development, with distinct sex-specific growth patterns and significant within-sex bone property variability. However, longitudinal studies are needed to evaluate how early skeletal growth impacts adult bone phenotypes and fracture risk. Metabolic and rare bone diseases amplify fracture risk, but the interplay between bone phenotypes and disease remains unclear. Although bone phenotyping is a promising approach to improve fracture risk assessment, the clinical availability of advanced imaging is still limited. Consequently, alternative strategies for assessing and managing fracture risk include vertebral fracture assessment from clinically available medical imaging modalities/techniques or from fracture risk assessment tools based on clinical risk factors. Bone fragility is not solely determined by its density but by a combination of bone geometry, distribution of bone mass, microarchitecture, and the intrinsic material properties of bone tissue. As such, different individuals can exhibit distinct bone phenotypes, which may predispose them to be more vulnerable or resilient to certain perturbations that influence bone strength.

Do bone turnover markers reflect changes in bone microarchitecture during treatment of patients with thyroid dysfunction?

PURPOSE: This study aimed to compare changes in the bone turnover markers (BTMs)-C-terminal telopeptide of type I collagen (CTX-I) and procollagen I N-terminal peptide (PINP)-with changes in the bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), during treatment of patients with thyroid dysfunction. METHODS: In women with newly diagnosed hypo- or hyperthyroidism, HR-pQCT variables, obtained from the tibia and the radius, were compared with BTMs. Data were collected at diagnosis and after at least 12 months of euthyroidism. RESULTS: 73 women completed the study (hypothyroidism, n = 27; hyperthyroidism, n = 46). Among hyperthyroid patients, correlations were found between changes in BTMs and HR-pQCT variables, primarily for cortical variables in the tibia, i.e. cortical thickness (CTX-I, p < 0.001; PINP, p < 0.001), and volumetric bone mass density (vBMD) (CTX-I, p < 0.001; PINP, p < 0.001). Moreover, correlations between BTMs and estimated bone strength were found. In the hypothyroid subgroup, no significant findings existed after adjustment. Following treatment, less decrease in tibial vBMD was seen among patients with increasing CTX-I compared to those with a decreasing CTX-I level (p = 0.009). Opposite findings applied to PINP, as patients with decreasing PINP showed an increase in tibial vBMD, in contrast to a decline in this parameter among patients with increasing PINP (p < 0.001). CONCLUSION: Changes in CTX-I and PINP correlated with HR-pQCT variables during the treatment of women with thyroid dysfunction. To some extent, these BTMs reflected the restoration of bone microarchitecture. CTX-I seems to be the most sensitive BTM in treatment-naïve thyroid diseases, while PINP is more useful for monitoring during treatment. TRIAL REGISTRATION NUMBER: NCT02005250. Date: December 9, 2013.

Bone Quality in Competitive Athletes: A Systematic Review.

The study objective was to assess bone quality measured by high resolution peripheral quantitative computed tomography (HR-pQCT) in competitive athletes. Medline, EMBASE and Sport Discus were searched through May 2022. Prior to submission, a follow-up database search was performed (January 2023). Studies of competitive athletes using HR-pQCT to assess bone quality were included. Athletes were aged between 14 and 45 years. Data extraction included study design and location (country), skeletal imaging modality and site, bone variables and any additional musculoskeletal-related outcome. Information identifying sports and athletes were also extracted. This review included 14 manuscripts and a total of 928 individuals (male: n=75; female: n=853). Athletes comprised 78% (n=722) of the included individuals and 93% of athletes were female. Assessment scores indicate the studies were good to fair quality. The athletes included in this review can be categorized into three groups: 1) healthy athletes, 2) athletes with compromised menstrual function (e.g., amenorrhoea), and 3) athletes with compromised bone health (e.g., bone stress injuries). When assessing bone quality using HR-pQCT, healthy competitive athletes had denser, stronger and larger bones with better microarchitecture, compared with controls. However, the same cannot be said for athletes with amenorrhoea or bone stress injuries.

Bone microstructure and volumetric bone mineral density in patients with global sagittal malalignment.

PURPOSE: Sagittal spinal malalignment often leads to surgical realignment, which is associated with major complications. Low bone mineral density (BMD) and impaired bone microstructure are risk factors for instrumentation failure. This study aims to demonstrate differences in volumetric BMD and bone microstructure between normal and pathological sagittal alignment and to determine the relationships among vBMD, microstructure, sagittal spinal and spinopelvic alignment. METHODS: A retrospective, cross-sectional study of patients who underwent lumbar fusion for degeneration was conducted. The vBMD of the lumbar spine was assessed by quantitative computed tomography. Bone biopsies were evaluated using microcomputed tomography (µCT). C7-S1 sagittal vertical axis (SVA; ≥ 50 mm malalignment) and spinopelvic alignment were measured. Univariate and multivariable linear regression analysis evaluated associations among the alignment, vBMD and µCT parameters. RESULTS: A total of 172 patients (55.8% female, 63.3 years, BMI 29.7 kg/m2, 43.0% with malalignment) including N = 106 bone biopsies were analyzed. The vBMD at levels L1, L2, L3 and L4 and the trabecular bone (BV) and total volume (TV) were significantly lower in the malalignment group. SVA was significantly correlated with vBMD at L1-L4 (ρ = -0.300, p < 0.001), BV (ρ = - 0.319, p = 0.006) and TV (ρ = - 0.276, p = 0.018). Significant associations were found between PT and L1-L4 vBMD (ρ = - 0.171, p = 0.029), PT and trabecular number (ρ = - 0.249, p = 0.032), PT and trabecular separation (ρ = 0.291, p = 0.012), and LL and trabecular thickness (ρ = 0.240, p = 0.017). In the multivariable analysis, a higher SVA was associated with lower vBMD (ß = - 0.269; p = 0.002). CONCLUSION: Sagittal malalignment is associated with lower lumbar vBMD and trabecular microstructure. Lumbar vBMD was significantly lower in patients with malalignment. These findings warrant attention, as malalignment patients may be at a higher risk of surgery-related complications due to impaired bone. Standardized preoperative assessment of vBMD may be advisable.