High-resolution Peripheral Quantitative Computed Tomography Research Articles

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

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. 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 12months of euthyroidism. 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). 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. NCT02005250. Date: December 9, 2013.

Impaired Bone Microarchitecture at Distal Radial and Tibial Reference Locations Is Not Related to Injury Site in Athletes With Bone Stress Injury

Background: Bone stress injuries (BSIs) are common sports injuries that occur because of an imbalance between microdamage accumulation and removal through bone remodeling. The underlying bone phenotype has been assumed to be a contributing factor. However, the bone microarchitecture of athletes with BSI is not well characterized, and no study has investigated whether impaired bone microarchitecture is associated with bone composition or anatomic site of injury. Purpose/Hypothesis: This cross-sectional study characterizes the bone microarchitecture at distal radial and tibial reference locations in athletes with BSI. Based on previous dual-energy X-ray absorptiometry (DXA) findings, the aim was to compare anatomic injury sites, hypothesizing that athletes with BSIs in bones with greater trabecular composition show impaired bone microarchitecture parameters compared with those with BSIs in bones with greater cortical composition. Study Design: Cohort study; Level of evidence, 3. Methods: Athletes who had presented to our outpatient clinic because of a high-grade BSI (ie, stress fracture) were retrospectively included. Blood and urine samples were collected. Areal bone mineral density (aBMD) was assessed by DXA at the lumbar spine and both hips. Bone microarchitecture was analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and tibia. HR-pQCT parameters were expressed in relation to available sex-, age-, and device-adjusted reference values and compared with a cohort of 53 age- and sex-matched controls. Results: In total, 53 athletes had a BSI of the foot (n = 20), tibia/fibula (n = 18), pelvis (n = 9), femur (n = 5), or sternum (n = 1). Based on DXA measurements, a Z-score of −1.0 or lower was found in 32 of 53 (60.4%) of the athletes, of whom 16 of 53 (30.2%) had a Z score −2.0 or lower. While an impairment of cortical area (P = .034 and P = .001) and thickness (P = .029 and P < .001) was detected at the distal radius and tibia in the BSI cohort compared with controls, no differences in BMD or bone microarchitecture were observed between anatomic injury sites. Furthermore, no difference was revealed when BSIs were grouped into cortical- and trabecular-rich sites. Conclusion: Reduced aBMD and impaired cortical bone microarchitecture were present in a considerable number of athletes with BSI. Neither aBMD nor bone microarchitecture was related to the injury site, highlighting the multifactorial etiology of BSI.

HR-pQCT parameters of the distal radius correlate with the bending strength of the radial diaphysis.

High resolution, peripheral quantitative computed tomography (HR-pQCT) scanners can now characterize an individual's trabecular architecture, cortical structure, and volumetric bone mineral density at a nominal resolution of 61μm. While predictions of failure load of the distal radius and tibial diaphysis in compression by finite element analysis (FEA) of HR-pQCT scans have been validated against mechanical tests of cadaveric bones in compression, namely for images with nominal resolutions of 82μm and 165μm, the HR-pQCT parameters that best predict bending strength of cortical bone remain unknown. Therefore, we scanned cadaveric forearms from 31 elderly donors (Female: 72.8±8.8years and Male: 72.1±6.3years), and then loaded the radial diaphysis to failure in three-point bending after denuding each bone (38 in total). The cortical parameters had stronger correlations with ultimate moment than the trabecular parameters such that cortical area and estimated failure load of the distal radius had the highest Spearman correlation coefficients (r=0.89 and r=0.81, respectively, p<0.0001). Despite being a known determinant of bone strength, cortical porosity of the distal radius did not correlate with ultimate moment (p=0.8537). In multivariate linear regressions with section modulus (SM) of the radial diaphysis as one of two predictors of bending strength, cortical area and cortical thickness were each significant contributors to the prediction of ultimate moment. Their contribution was one-half and one-third, respectively, of the contribution from SM. None of the HR-pQCT parameters were strongly correlated with post-yield displacement, an indicator of bone brittleness. In support of HR-pQCT imaging of the distal radius to identify individuals with osteoporosis, the present study found that parameters of the cortex and failure load predictions by linear FEA are strongly related to the bending strength of cortical bone.

Imaging techniques to study diabetic bone disease.

This review article presents the most recent research on bone fragility in individuals with diabetes from a medical imaging perspective. The widespread availability of dual-energy X-ray absorptiometry (DXA) and trabecular bone score (TBS) software has led to recent assessments of bone fragility with this texture parameter in several studies of type 2 diabetes mellitus (T2D), but in few of type 1 diabetes mellitus (T1D). Although most studies show a trend of reduced TBS values in T2D independent of areal bone mineral density (aBMD) of the lumbar spine, some studies also show the limitations of TBS in both T2D and T1D. Given the limitations of DXA to assess bone strength and investigate the etiology of bone fragility in diabetes, more investigators are incorporating three-dimensional (3D) medical imaging techniques in their studies. Recent use of 3D medical imaging to assess bone fragility in the setting of diabetes has been mostly limited to a few cross-sectional studies predominantly incorporating high-resolution peripheral quantitative computed tomography (HR-pQCT). Although HR-pQCT studies indicate higher tibial cortical porosity in subjects with T2D, results are inconsistent in T1D due to differences in study designs, sample sizes, and subject characteristics, among other factors. With respect to central CT, recent studies support a previous finding in the literature indicating femoral neck geometrical impairments in subjects with T2D and provide encouraging results for the incorporation of finite element analysis (FEA) to assess bone strength in studies of T2D. In the recent literature, there are no studies assessing bone fragility in T1D with QCT, and only two studies used pQCT reporting tibial and radial impairments in young women and children with T1D, respectively. Magnetic resonance imaging (MRI) has not been recently used in diabetic studies of bone fragility. As bone fragility in diabetes is not explained by DXA-derived aBMD and given the limitations of cross-sectional studies, it is imperative to use 3D imaging techniques for longitudinal assessments of the density, quality, and microenvironment of bone to improve our understanding of the effects of diabetes on bone and reduce the risk of fracture in this large and vulnerable population of subjects with diabetes.

Compartment-specific effects of muscle strength on bone microarchitecture in women at high risk of osteoporosis.

BackgroundIt is well known that skeletal integrity is influenced by the musculature. Poor muscle strength (i.e. sarcopenia) is considered a major predictor of fragility fractures. While this observation appears particularly relevant for older women with increased risk of osteoporosis, there has been no comprehensive investigation to determine the influence of muscle performance on compartment‐specific bone microarchitecture in multiple body regions.MethodsWe retrospectively analysed data from different muscle performance and bone microarchitecture assessments in 230 women (aged 21 to 87 years) at high risk of osteoporosis. Muscle performance tests included grip strength and chair rising test (CRT) combined with mechanography. Balance was determined by Romberg posturography. Areal bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry (DXA) at the hip and lumbar spine. Compartment‐specific volumetric BMD, microarchitecture, and geometry were assessed by second‐generation high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at multiple skeletal sites (distal radius, tibia, and fibula). Regression models were applied to test for interactions between muscle and bone parameters. Subgroups were defined to compare women with osteoporosis and osteosarcopenia regarding BMD and microarchitecture.ResultsWhile osteoporosis was diagnosed in 115/230 (50.0%) women, sarcopenia was detected in 38/230 (16.5%). Positive associations of both grip strength and CRT maximum force with cortical geometric and microarchitectural parameters were detected at all measured sites, with the strongest effect applying to CRT maximum force and tibial parameters (e.g. tibial cortical area R 2 = 0.36, P < 0.0001, and tibial cortical thickness R 2 = 0.26, P < 0.0001). Balance parameters showed much weaker or no associations with HR‐pQCT parameters. Major associations between muscle strength and trabecular parameters could not be confirmed. Age and body mass index were confirmed as negative and positive predictors for several microarchitectural parameters, respectively. An independent predictive value of grip strength on radial, tibial, and fibular (all P < 0.01) cortical area and of CRT maximum relative force on cortical thickness (all P < 0.05) was revealed. Women with osteosarcopenia showed significantly reduced cortical HR‐pQCT parameters but no differences in DXA values compared with women with osteoporosis but no sarcopenia. Stratification by fracture and treatment status revealed that vertebral fractures and denosumab treatment altered the muscle–bone interaction.ConclusionsA systemic interaction between muscle strength and bone microarchitecture was demonstrated, and this interaction appears to be primarily with the cortical bone compartment. The value of muscle assessments in fracture risk evaluation may be partly mediated by their effects on bone microarchitecture.

What Is the Diagnostic Performance of Conventional Radiographs and Clinical Reassessment Compared With HR-pQCT Scaphoid Fracture Diagnosis?

Conventional radiographs and clinical reassessment are considered guides in managing clinically suspected scaphoid fractures. This is a unique study as it assessed the value of conventional radiographs and clinical reassessment in a cohort of patients, all of whom underwent additional imaging, regardless of the outcome of conventional radiographs and clinical reassessment. (1) What is the diagnostic performance of conventional radiographs in patients with a clinically suspected scaphoid fracture compared with high-resolution peripheral quantitative CT (HR-pQCT)? (2) What is the diagnostic performance of clinical reassessment in patients with a clinically suspected scaphoid fracture compared with HR-pQCT? (3) What is the diagnostic performance of conventional radiographs and clinical reassessment combined compared with HR-pQCT? Between December 2017 and October 2018, 162 patients with a clinically suspected scaphoid fracture presented to the emergency department (ED). Forty-six patients were excluded and another 25 were not willing or able to participate, which resulted in 91 included patients. All patients underwent conventional radiography in the ED and clinical reassessment 7 to 14 days later, together with CT and HR-pQCT. The diagnostic performance characteristics and accuracy of conventional radiographs and clinical reassessment were compared with those of HR-pQCT for the diagnosis of fractures since this was proven to be superior to CT scaphoid fracture detection. The cohort included 45 men and 46 women with a median (IQR) age of 52 years (29 to 67). Twenty-four patients with a median age of 44 years (35 to 65) were diagnosed with a scaphoid fracture on HR-pQCT. When compared with HR-pQCT, conventional radiographs alone had a sensitivity of 67% (95% CI 45% to 84%), specificity of 85% (95% CI 74% to 93%), positive predictive value (PPV) of 62% (95% CI 46% to 75%), negative predictive value (NPV) of 88% (95% CI 80% to 93%), and a positive and negative likelihood ratio (LR) of 4.5 (95% CI 2.4 to 8.5) and 0.4 (95% CI 0.2 to 0.7), respectively. Compared with HR-pQCT, clinical reassessment alone resulted in a sensitivity of 58% (95% CI 37% to 78%), specificity of 42% (95% CI 30% to 54%), PPV of 26% (95% CI 19% to 35%), NPV of 74% (95% CI 62% to 83%), as well as a positive and negative LR of 1.0 (95% CI 0.7 to 1.5) and 1.0 (95% CI 0.6 to 1.7), respectively. Combining clinical examination with conventional radiography produced a sensitivity of 50% (95% CI 29% to 71%), specificity of 91% (95% CI 82% to 97%), PPV of 67% (95% CI 46% to 83%), NPV of 84% (95% CI 77% to 88%), as well as a positive and negative LR of 5.6 (95% CI 2.4 to 13.2) and 0.6 (95% CI 0.4 to 0.8), respectively. The accuracy of conventional radiographs (80% compared with HR-pQCT) and clinical reassessment (46% compared with HR-pQCT) indicate that the value of clinical reassessment is limited in diagnosing scaphoid fractures and cannot be considered directive in managing scaphoid fractures. The combination of conventional radiographs and clinical reassessment does not increase the accuracy of these diagnostic tests compared with the accuracy of conventional radiographs alone and is therefore also limited in diagnosing scaphoid fractures. Level II, diagnostic study.

Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers.

Background: Nephrolithiasis has been associated with bone loss and vascular calcification (VC), reflecting abnormal extraosseous calcium deposition. Fetuin-A (Fet-A) acts as a potent inhibitor of ectopic mineralization. The aim of the present study was to evaluate the prevalence of VC in stone formers (SF) and non-stone formers (NSF) and to investigate potential determinants of VC among SF, including circulating levels of Fet-A and bone microarchitecture parameters. Methods: Abdominal aortic calcification (AAC) was assessed using available computed tomography in SF and in age-, sex-, and BMI-matched NSF (potential living kidney donors). Serum Fet-A was measured in stored blood samples from SF. Bone microarchitecture parameters were obtained as a post hoc analysis of a cross-sectional cohort from young SF evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: A total of 62 SF (38.0 [28.0–45.3] years old) and 80 NSF (40.0 [37.0–45.8] years old) were included. There was no significant difference in AAC scores between SF and NSF. However, when dividing SF according to mean AAC score, below <5.8% (n = 33) or above ≥5.8% (n = 29), SF with higher AAC presented significantly higher BMI and tibial cortical porosity (Ct.Po) and significantly lower serum HDL, klotho, Fet-A, and eGFR. Urinary calcium did not differ between groups, but fractional excretion of phosphate was higher in the former. Upon multivariate regression, BMI, serum Fet-A, and tibial Ct.Po remained independently associated with AAC. Conclusions: This study suggests an association between reduced circulating Fet-A levels and increased bone Ct.Po with VC in SF.

Bone Response to Weight Loss Following Bariatric Surgery

Obesity is a global health challenge that warrants effective treatments to avoid its multiple comorbidities. Bariatric surgery, a cornerstone treatment to control bodyweight excess and relieve the health-related burdens of obesity, can promote accelerated bone loss and affect skeletal strength, particularly after malabsorptive and mixed surgical procedures, and probably after restrictive surgeries. The increase in bone resorption markers occurs early and persist for up to 12 months or longer after bariatric surgery, while bone formation markers increase but to a lesser extent, suggesting a potential uncoupling process between resorption and formation. The skeletal response to bariatric surgery, as investigated by dual-energy X-ray absorptiometry (DXA), has shown significant loss in bone mineral density (BMD) at the hip with less consistent results for the lumbar spine. Supporting DXA studies, analyses by high-resolution peripheral quantitative computed tomography (HR-pQCT) showed lower cortical density and thickness, higher cortical porosity, and lower trabecular density and number for up to 5 years after bariatric surgery. These alterations translate into an increased risk of fall injury, which contributes to increase the fracture risk in patients who have been subjected to bariatric surgery procedures. As bone deterioration continues for years following bariatric surgery, the fracture risk does not seem to be dependent on acute weight loss but, rather, is a chronic condition with an increasing impact over time. Among the post-bariatric surgery mechanisms that have been claimed to act globally on bone health, there is evidence that micro- and macro-nutrient malabsorptive factors, mechanical unloading and changes in molecules partaking in the crosstalk between adipose tissue, bone and muscle may play a determining role. Given these circumstances, it is conceivable that bone health should be adequately investigated in candidates to bariatric surgery through bone-specific work-up and dedicated postsurgical follow-up. Specific protocols of nutrients supplementation, motor activity, structured rehabilitative programs and, when needed, targeted therapeutic strategies should be deemed as an integral part of post-bariatric surgery clinical support.

Bone microstructure evaluated by TBS and HR-pQCT in Chinese adults with X-linked hypophosphatemia

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Although generalized mineralization defects have been observed, elevated areal bone mineral density (aBMD) in the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) has also been found in XLH. In contrast, high-resolution peripheral quantitative computed tomography (HR-pQCT) revealed lower volumetric BMD (vBMD) and damaged bone microstructure in the peripheral bone in XLH. Trabecular bone score (TBS), which can assess the trabecular microstructure in the lumbar spine, has not been explored in XLH. This study aimed to explore TBS and its correlations with biochemical indices and HR-pQCT parameters in adult XLH patients. A total of 66 patients with XLH (26 men and 40 women) aged 29.6±9.6years and 66 age- and sex-matched healthy controls were included. Z score of lumbar spine aBMD was relatively high [2.0 (0.6, 3.7)], with normal TBS (1.475±0.129) in the XLH patients. HR-pQCT revealed larger total and trabecular area in the peripheral bone in the XLH group compared with the control group. In addition, lower trabecular and cortical vBMD, lower trabecular number with greater separation, and lower bone strength at both the radius and tibia were found in the XLH group compared with the control group. Smaller cortical area, lower thickness and higher porosity in the XLH group compared with controls were only found at the radius. TBS was not associated with any biochemical indices, while better HR-pQCT parameters correlated with higher serum phosphate and lower ALP levels. TBS was positively related with aBMD but not HR-pQCT parameters. In conclusion, adult patients with XLH had high bone mass and normal TBS in the lumbar spine but compromised microarchitecture and bone strength in the peripheral bone. This finding indicated a site-specific effect of the disease on the skeleton in the XLH patients.

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study.

The effects of daily teriparatide (20μg) (D-PTH), weekly high-dose teriparatide (56.5μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients. The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18months' treatment compared with baseline. DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%). D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH.

Na-Cl Co-transporter (NCC) gene inactivation is associated with improved bone microstructure.

To evaluate the impact of the inactivation of NCC on bone turnover and microarchitecture in Gitelman syndrome patients. A cross-sectional study was conducted in 45 GS patients (25 males and 20 females). Serum procollagen type 1N-terminal propeptide (P1NP), β-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX), and osteocalcin were measured. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in GS patients and age- and sex-matched healthy controls. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. GS patients had a relatively lower level of β-CTX. aBMD at several skeletal sites was improved in GS patients. HR-pQCT assessment revealed that GS patients had slightly thinner but significantly more compact trabecular bone (increased trabecular number and decreased thickness), notably decreased cortical porosity, and increased volume BMD (vBMD) at both the radius and tibia compared with controls. The disease severity, represented as the relationship with the minimum level of magnesium during the course and standard base excess, was associated with bone microarchitecture parameters after adjusting for age, sex, and BMI. The decreased vBMD and Tb.BV/TV, and increased Tb.Sp and Ct.Po with aging, were reversed in GS patients to a certain extent. GS patients have superior bone microarchitecture, which suggests that the inactivation of NCC might be beneficial for avoiding osteoporosis.

Lower hand grip in rheumatoid arthritis patients is associated with low finite element analysis using high resolution peripheral quantitative computed tomography scan of the 2nd metacarpophalangeal joint.

To evaluate hand function by hand grip test in rheumatoid arthritis (RA) patients, and its association with bone erosions and the estimated bone strength (finite element - FE analysis) through the analysis of the 2nd metacarpal head of the dominant hand using high resolution peripheral quantitative computed tomography (HR-pQCT). Eighty-two female RA patients between 18-50 years old were selected. Demographic data, Health Questionnaire Assessment Disability Index (HAQ), Disease Activity Score of 28 joints (DAS)-28, simplified disease activity index (SDAI) and the hand grip test were set. The HR-pQCT scans of 2nd metacarpophalangeal joints of the dominant hand of all patients were performed according to SPECTRA group protocols. The images were used to assess bone erosions and FE analysis. The hand grip test was categorized in 2 groups and separately compared (< 18 vs ≥18 kgf). A logistic regression was performed using hand grip test <18 kgf as a dependent variable. A significant difference was found between the 2 groups regarding HAQ, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein), DAS-28, SDAI, total volume of erosion and bone strength parameter (FE analysis - Failure Load [F.Load]). The logistic regression analysis showed that the risk factors associated with hand grip test <18 kgf were higher SDAI (odds ratio [OR] 0.912; 95% CI 0.837-0.993) and lower values of bone strength parameter (F.Load) (OR 1.007; 95% CI 1.002-1.012). Lower values of hand grip test were associated with higher disease activity score-SDAI and lower bone strength of 2nd metacarpal bone head of the dominant hand evaluated here through a FE analysis using HR-pQCT scan.

Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial.

In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking. This study aimed to determine the effects of E2 on bone health in men in the absence of endogenous T. This study is a 6-month randomized, placebo-controlled trial with the hypothesis that E2 would slow the decline of volumetric bone mineral density (vBMD) and bone microstructure, maintain areal bone mineral density (aBMD), and reduce bone remodelling. 78 participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel daily or matched placebo. The outcome measures were vBMD and microarchitecture at the distal tibia and distal radius by high-resolution peripheral quantitative CT, aBMD at the spine and hip by dual-energy x-ray absorptiometry, and serum bone remodelling markers. For the primary endpoint, total vBMD at the distal tibia, there was no significant difference between groups, mean adjusted difference (MAD) 2.0 mgHA/cm3 (95% CI: -0.8 to 4.8), P = 0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8 mgHA/cm3 (95% CI: 4.5 to 25.0), P = 0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250 N (95% CI: 36 to 465), P = 0.02, and radius, MAD 193 N (95% CI: 65 to 320), P = 0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02 g/cm2 (95% CI: 0.01 to 0.03), P = 0.01, and ultra-distal radius, MAD 0.01 g/cm2 (95% CI: 0.00 to 0.02), P = 0.01, and reduced serum bone remodelling markers. Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.

Physiologic Transdermal Estradiol Replacement Mimics Effects of Endogenous Estrogen on Bone Outcomes in Hypoestrogenic Women with Anorexia Nervosa.

Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14–25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were −1.13 (−1.58, −0.38) in AN-E+ vs. 0.08 (−0.40, 0.84) in HC (p < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.

Relationships between QUS and HR-pQCT, DXA, and bone turnover markers.

Relationship of quantitative ultrasound (QUS) with high-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers was analyzed. The subjects were 480 individuals. Speed of sound (SOS) was measured by calcaneal QUS. Volumetric bone mineral density (vBMD) and microarchitecture of trabecular and cortical bone in the distal radius and tibia were assessed by HR-pQCT. Areal bone mineral density (aBMD) in the lumbar spine and proximal femur were measured by DXA. TRACP-5b, P1NP, 25 (OH) vitamin D, and pentosidine were evaluated by biochemical tests. The correlation of each parameter was analyzed for all subjects and by sex and age group. QUS was moderately correlated with Tb.vBMD and Tb.BV/TV in the radius and tibia. No correlation was seen with Ct.vBMD or cortical porosity (Ct.Po). Although a correlation was seen with cortical thickness (Ct.Th) in the tibia in all subjects, no correlation was seen in women aged ≥ 60years. QUS showed moderate correlations with aBMD in the proximal femur. Although moderate correlation was seen with aBMD in the lumbar spine in all subjects, no correlation was seen in subjects aged ≥ 60years. No significant correlations were seen between QUS and biochemical markers. Moderate correlations were seen between QUS and Tb.vBMD and microarchitecture in the radius and tibia and aBMD of the proximal femur. On the other hand, practically no correlations were seen with Ct.vBMD or Ct.Po and the bone-related biochemical markers. Only in middle age, moderate correlations were seen with Ct.Th in the tibia and with aBMD of the lumbar spine.

Changes in volumetric bone mineral density and bone quality after Roux-en-Y gastric bypass: A meta-analysis with meta-regression.

SummaryThis meta‐analysis aimed to assess the effect of Roux‐en‐Y gastric bypass (RYGB) on three‐dimensionally assessed volumetric bone mineral density (vBMD) with the effect of time on these changes, on bone quality, and the agreement of dual‐energy X‐ray absorptiometry (DXA) with quantitative computed tomography (QCT) or high‐resolution peripheral QCT (HR‐pQCT) estimates of bone loss. We searched PubMed, Web of Science, Cochrane, Scopus, and EBSCO. Longitudinal studies on adults undergoing RYGB in which vBMD was assessed by QCT or HR‐pQCT with ≥6 months follow‐up were included. Total hip (TH) changes were reported in four studies, lumbar spine (LS) in eight, radius in eight, and tibia in seven. Significant post‐RYGB vBMD reductions occurred at all skeletal sites analyzed. Meta‐regression revealed that time post‐RYGB was significantly associated with vBMD deterioration in all skeletal sites except at the TH. RYGB also led to significant deterioration on bone quality. DXA underestimated LS and overestimated TH bone losses post‐RYGB. In conclusion, RYGB was associated with significant vBMD loss, which makes screening of bone mass progression by three‐dimensional technology a crucial clinical issue to prevent fracture risk and osteoporosis.

Impact of GH administration on skeletal endpoints in adults with overweight/obesity.

Overweight/obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity. An 18-month, randomized, double-blind, placebo-controlled study of GH, followed by 6-month observation. In this study, 77 adults (53% men), aged 18-65 years, BMI ≥ 25 kg/m2, and BMD T- or Z-score ≤ -1.0 were randomized to daily subcutaneous GH or placebo, targeting IGF1 in the upper quartile of the age-appropriate normal range. Forty-nine completed 18 months. DXA, volumetric quantitative CT, and high-resolution peripheral quantitative CT were performed. Pre-treatment mean age (48 ± 12 years), BMI (33.1 ± 5.7 kg/m2), and BMD were similar between groups. P1NP, osteocalcin, and CTX increased (P < 0.005) and visceral adipose tissue decreased (P = 0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased in the GH vs placebo group (P < 0.05). Between 18 and 24 months (post-treatment observation period), radius aBMD and tibia cortical thickness increased in the GH vs placebo group. At 24 months, there were no differences between the GH and placebo groups in bone density, structure, or strength compared to baseline. GH administration for 18 months increased bone turnover in adults with overweight/obesity. It also decreased some measures of BMD, bone microarchitecture, and bone strength, which all returned to pre-treatment levels 6 months post-therapy. Whether GH administration increases BMD with longer treatment duration, or after mineralization of an expanded remodeling space post-treatment, requires further investigation.

Thiazide use and skeletal microstructure: Results from a multi-ethnic study

BackgroundThiazide diuretics, a commonly used class of anti-hypertensives, have been associated with increased areal bone mineral density (aBMD). Data regarding effects on fracture are conflicting and no information is available regarding effects on skeletal microstructure and mechanical competence. MethodsWe compared skeletal microstructure, volumetric BMD (vBMD), stiffness and prevalent fractures in current thiazide diuretic users and non-users from a population-based multiethnic cohort of elderly adults age ≥ 65 years (N = 599) with high resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis. ResultsFemale current thiazide diuretic users had higher weight and BMI and were more likely to be non-Caucasian compared to non-users. There were no differences in age, historical fractures or falls between female users and non-users. Female thiazide users tended to have lower calcium and vitamin d intake compared to non-users. After adjusting for age, weight, race and other covariates, 1/3-radius mean aBMD by dual energy x-ray absorptiometry (DXA) was 3.2% (p = 0.03) higher in female users vs. non-users. By HRpQCT, adjusted mean cortical vBMD was 2.4% (p = 0.03) higher at the radius in female users vs. non-users, but there was no difference in stiffness. DXA results were similar in the subset of Black females. There was no difference in any adjusted aBMD or cortical skeletal parameters by DXA or HRpQCT respectively in males. ConclusionsThiazide use was associated with a modestly higher aBMD at the predominantly cortical 1/3-radius site and radial cortical vBMD by HRpQCT in females. The effect on cortical bone may offer skeletal benefits in women taking thiazides for other indications such as hypertension, hypercalciuria or recurrent nephrolithiasis.

MO542: Bone Mineral Density, Bone Micro-Architecture Evolution After Kidney Transplantation: A Prospective Cohort Study

Abstract BACKGROUND AND AIMS Bone loss and mineral abnormalities are frequent in kidney transplant recipients (KTRs) and associated with a high risk of fracture, cardiovascular mortality and an increase in health care costs. In daily clinics, the detection of bone abnormalities after transplantation includes bone biomarkers and imaging technique [Dual Energy X-ray (DEXA)] to assess respectively the bone turnover and the bone mineral density (BMD), but with limitations. The high-resolution peripheral quantitative computed tomography (HR-pQCT) provides additional noninvasive information on bone microarchitecture and BMD with a better distinction between cortical and trabecular areas. The goal of our study is to evaluate the evolution of bone structure using HR-pQCT compared to standard technique (DXA) in a prospective cohort of KTRs. METHOD All patients referred for a single kidney transplant at the university hospital of Liège with no history of exposure to antiresorptive agents were eligible for inclusion (NCT04713774). Participants underwent baseline and 3-month biomarkers analysis, BMD measurements by DEXA. HR-pQCT images were obtained of the distal radius and distal tibia (non-dominant, non-fractured limb) using the XtremeCT device with standard protocols. HR-pQCT assessed quantitative measurement of the volumetric density of trabecular and cortical bone as well as bone structure (trabecular number or thickness or cortical porosity for instance). RESULTS A total of 26 patients were prospectively included. The mean age was 57.3 ± 12.1 years. The mean dialysis vintage was 27.5 ± 16.4 months before transplantation. Bone biomarkers showed a significant decrease at 3 months after transplantation. PTH decreased from 221.72 ng/L to 59.6 ng/L (P &amp;lt; 0.0001), P1NP from 211 ug/L to 72 ug/L (P &amp;lt; 0.013) and BLAP from 23 ug/L to 13 ug/L (P = 0.042). BMD was measured by DXA and HR-pQCT at 7 days [6; 8] and 102 days (90; 113) after transplantation. We observed a significant reduction of BMD by DXA at the hip site from 0.868 g/cm2 to 0.856 g/cm2 (P = 0.02), but not at the lumbar site. The HR-pQCT analysis demonstrated a significant reduction of the trabecular BMD from 152.62 mg HA/ccm to 150.80 mg HA/ccm (P &amp;lt; 0.0001) at the tibia site and from 159.09 mg HA/ccm to 156.25 mg HA/ccm (P &amp;lt; 0.0001) at the radius site. No change in bone structure have been observed at 3 months post-transplantation with the HR-pQCT analysis. CONCLUSION HR-pQCT is sensitive enough to show a significant decrease of BMD at the trabecular site, as soon as 3 months after transplantation compared to DEXA at the lumbar spine. However, no change in bone structure nor cortical bone volume has been observed. The sensibility of this technique might be higher than DEXA. The rapid assessment of bone structure (3 months post-transplantation) might be too soon to evaluate such abnormalities. Detecting properly rapid changes in bone density, as soon as 3 months after renal transplantation seems feasible. The impact on bone health management needs to be further studied.

Sedentary behavior is associated with poorer bone microarchitecture at the distal tibia in older patients as assessed via high-resolution peripheral quantitative computed tomography (HR-pQCT)

Sedentary behavior is associated with poorer bone microarchitecture at the distal tibia in older patients as assessed via high-resolution peripheral quantitative computed tomography (HR-pQCT)