Effects on bone geometry,density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: A case‐control study using HR‐pQCT

Patients with primary hyperparathyroidism (PHPT) have continuously elevated parathyroid hormone (PTH) and consequently increased bone turnover with negative effects on cortical (Ct) bone with preservation of trabecular (Tb) bone. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new technique for in vivo assessment of geometry, volumetric density, and microarchitecture at the radius and tibia. In this study we aimed to evaluate bone status in women with PHPT compared with controls using HR‐pQCT. The distal radius and tibia of 54 women—27 patients with PHPT (median age 60, range 44–75 years) and 27 randomly recruited age‐matched healthy controls (median age 60, range 44–76 years)—were imaged using HR‐pQCT along with areal bone mineral density (aBMD) by dual‐energy X‐ray absorptiomentry (DXA) of the ultradistal forearm, femoral neck, and spine (L1–L4). Groups were comparable regarding age, height, and weight. In the radius, patients had reduced Ct area (Ct.Ar) (p = .008), Ct thickness (Ct.th) (p = .01) along with reduced total (p = .002), Ct (p = .02), and Tb (p = .02) volumetric density and reduced Tb number (Tb.N) (p = .04) and increased Tb spacing (Tb.sp) (p = .05). Ct porosity did not differ. In the tibia, no differences in HR‐pQCT parameters were found. Moreover, patients had lower ultradistal forearm (p = .005), spine (p = .04), and femoral neck (p = 0.04) aBMD compared with controls. In conclusion, a negative bone effect of continuously elevated PTH with alteration of HR‐pQCT assessed geometry, volumetric density, and both trabecular and cortical microarchitecture in radius but not tibia was found along with reduced aBMD by DXA at all sites in female patients with PHPT. © 2010 American Society for Bone and Mineral Research     

Compromised trabecular microarchitecture and lower finite element estimates of radius and tibia bone strength in adults with turner syndrome: a cross-sectional study using high-resolution-pQCT

Although bone mass appear ample for bone size in Turner syndrome (TS), epidemiological studies have reported an increased risk of fracture in TS. We used high‐resolution peripheral quantitative computed tomography (HR‐pQCT) to measure standard morphological parameters of bone geometry and microarchitecture, as well as estimated bone strength by finite element analysis (FEA) to assess bone characteristics beyond bone mineral density (BMD) that possibly contribute to the increased risk of fracture. Thirty‐two TS patients (median age 35, range 20–61 years) and 32 healthy control subjects (median age 36, range 19–58 years) matched with the TS participants with respect to age and body‐mass index were studied. A full region of interest (ROI) image analysis and a height‐matched ROI analysis adjusting for differences in body height between groups were performed. Mean bone cross‐sectional area was lower in TS patients in radius (?15%) and tibia (?13%) (both p < 0.01) whereas cortical thickness was higher in TS patients in radius (18%, p < 0.01) but not in tibia compared to controls. Cortical porosity was lower in TS patients at both sites (?32% in radius, ?36% in tibia, both p < 0.0001). Trabecular integrity was compromised in TS patients with lower bone volume per tissue volume (BV/TV) (?27% in radius, ?22% in tibia, both p < 0.0001), trabecular number (?27% in radius, ?12% in tibia, both p < 0.05), and higher trabecular spacing (54% in radius, 23% in tibia, both p < 0.01). In the height‐matched ROI analysis, differences remained significant apart from total area at both sites, cortical thickness in radius, and trabecular number in tibia. FEA estimated failure load was lower in TS patients in both radius (?11%) and tibia (?16%) (both p < 0.01) and remained significantly lower in the height‐matched ROI analysis. Conclusively, TS patients had compromised trabecular microarchitecture and lower bone strength at both skeletal sites, which may partly account for the increased risk of fracture observed in these patients. © 2012 American Society for Bone and Mineral Research.     

Relationship between vitamin D status and bone mineralization,mass, and metabolism in children with osteogenesis imperfecta: Histomorphometric study

The effect of low vitamin D levels in children with bone fragility disorders has not been examined in detail. In this study, we evaluated the relationship between vitamin D status and parameters of skeletal mineralization, mass, and metabolism in a group of pediatric osteogenesis imperfecta (OI) patients. This retrospective study consisted of 71 patients with a diagnosis of OI type I, III, or IV (ages 1.4 to 17.5 years; 36 girls) who had not received bisphosphonate treatment before iliac bone biopsy. Serum 25‐hydroxyvitamin D [25(OH)D] levels ranged from 13 to 103 nmol/L and were less than 50 nmol/L in 37 patients (52%). None of the OI patients had radiologic signs of rickets or fulfilled the histomorphometric criteria for the diagnosis of osteomalacia (ie, elevated results for both osteoid thickness and mineralization lag time). Serum 25(OH)D levels were negatively correlated with age and serum parathyroid hormone levels but were not correlated with any parameter of bone mineralization (ie, osteoid thickness, mineralization lag time, or bone‐formation rate per bone surface) or bone mass (ie, lumbar spine areal bone mineral density, iliac bone volume per tissue volume, or iliac cortical width). We found no evidence that serum 25(OH)D levels in the range from 13 to 103 nmol/L were associated with measures of bone mineralization, metabolism, or mass in children with OI. © 2011 American Society for Bone and Mineral Research     

Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: an HR-pQCT study

The aim of this study was to determine the sex- and maturity-related differences in bone microstructure and estimated bone strength at the distal radius and distal tibia in children and adolescents. We used high-resolution pQCT to measure standard morphological parameters in addition to cortical porosity (Ct.Po) and estimated bone strength by finite element analysis. Participants ranged in age from 9 to 22 years (n = 212 girls and n = 186 boys) who were scanned annually for either one (11%) or two (89%) years at the radius and for one (15%), two (39%), or three (46%) years at the tibia. Participants were grouped by the method of Tanner into prepubertal, early pubertal, peripubertal, and postpubertal groups. At the radius, peri- and postpubertal girls had higher cortical density (Ct.BMD; 9.4% and 7.4%, respectively) and lower Ct.Po (-118% and -56%, respectively) compared with peri- and postpubertal boys (all p < 0.001). Peri- and postpubertal boys had higher trabecular bone volume ratios (p < 0.001) and larger cortical cross-sectional areas (p < 0.05, p < 0.001) when compared with girls. Based upon the load-to-strength ratio (failure load/estimated fall force), boys had lower risk of fracture than girls at every stage except during early puberty. Trends at the tibia were similar to the radius with differences between boys and girls in Ct.Po (p < 0.01) and failure load (p < 0.01) at early puberty. Across pubertal groups, within sex, the most mature girls and boys had higher Ct.BMD and lower Ct.Po than their less mature peers (prepuberty) at both the radius and tibia. Girls in early, peri-, and postpubertal groups and boys in peri- and postpubertal groups had higher estimates of bone strength compared with their same-sex prepubertal peers (p < 0.001). These results provide insight into the sex- and maturity-related differences in bone microstructure and estimated bone strength.     

Bone Microarchitecture Assessed by HR‐pQCT as Predictor of Fracture Risk in Postmenopausal Women: The OFELY Study

Several cross‐sectional studies have shown that impairment of bone microarchitecture contributes to skeletal fragility. The aim of this study was to prospectively investigate the prediction of fracture (Fx) by bone microarchitecture assessed by high‐resolution peripheral computed tomography (HR‐ pQCT) in postmenopausal women. We measured microarchitecture at the distal radius and tibia with HR‐pQCT in the OFELY study, in addition to areal BMD with dual‐energy X‐ray absorptiometry (DXA) in 589 women, mean ± SD age 68 ± 9 years. During a median [IQ] 9.4 [1.0] years of follow‐up, 135 women sustained an incident fragility Fx, including 81 women with a major osteoporotic Fx (MOP Fx). After adjustment for age, women who sustained Fx had significantly lower total and trabecular volumetric densities (vBMD) at both sites, cortical parameters (area and thickness at the radius, vBMD at the tibia), trabecular number (Tb.N), connectivity density (Conn.D), stiffness, and estimated failure load at both sites, compared with control women. After adjustment for age, current smoking, falls, prior Fx, use of osteoporosis‐related drugs, and total hip BMD, each quartile decrease of several baseline values of bone microarchitecture at the radius was associated with significant change of the risk of Fx (HR of 1.39 for Tb.BMD [p = 0.001], 1.32 for Tb.N [p = 0.01], 0.76 for Tb.Sp.SD [p = 0.01], 1.49 [p = 0.01] for Conn.D, and 1.27 for stiffness [p = 0.02]). At the tibia, the association remained significant for stiffness and failure load in the multivariate model for all fragility Fx and for Tt.BMD, stiffness, and failure load for MOP Fx. We conclude that impairment of bone microarchitecture—essentially in the trabecular compartment of the radius—predict the occurrence of incident fracture in postmenopausal women. This assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone, to benefit from a therapeutic intervention. © 2017 American Society for Bone and Mineral Research.     

A longitudinal HR‐pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density,cortical and trabecular microarchitecture,biomechanics, and bone turnover

The goal of this study was to characterize longitudinal changes in bone microarchitecture and function in women treated with an established antifracture therapeutic. In this double‐blind, placebo‐controlled pilot study, 53 early postmenopausal women with low bone density (age = 56 ± 4 years; femoral neck T‐score = ?1.5 ± 0.6) were monitored by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) for 24 months following randomization to alendronate (ALN) or placebo (PBO) treatment groups. Subjects underwent annual HR‐pQCT imaging of the distal radius and tibia, dual‐energy X‐ray absorptiometry (DXA), and determination of biochemical markers of bone turnover (BSAP and uNTx). In addition to bone density and microarchitecture assessment, regional analysis, cortical porosity quantification, and micro‐finite‐element analysis were performed. After 24 months of treatment, at the distal tibia but not the radius, HR‐pQCT measures showed significant improvements over baseline in the ALN group, particularly densitometric measures in the cortical and trabecular compartments and endocortical geometry (cortical thickness and area, medullary area) (p < .05). Cortical volumetric bone mineral density (vBMD) in the tibia alone showed a significant difference between treatment groups after 24 months (p < .05); however, regionally, significant differences in Tb.vBMD, Tb.N, and Ct.Th were found for the lateral quadrant of the radius (p < .05). Spearman correlation analysis revealed that the biomechanical response to ALN in the radius and tibia was specifically associated with changes in trabecular microarchitecture (|ρ| = 0.51 to 0.80, p < .05), whereas PBO progression of bone loss was associated with a broad range of changes in density, geometry, and microarchitecture (|ρ| = 0.56 to 0.89, p < .05). Baseline cortical geometry and porosity measures best predicted ALN‐induced change in biomechanics at both sites (ρ > 0.48, p < .05). These findings suggest a more pronounced response to ALN in the tibia than in the radius, driven by trabecular and endocortical changes. © 2010 American Society for Bone and Mineral Research.     

Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: An in vivo HR‐pQCT study

Increases in cortical porosity (Ct.Po) and decreases in cortical thickness (Ct.Th) are associated with increased bone fragility. The purpose of this study was to validate an autosegmentation method for high‐resolution peripheral quantitative computed tomography (HR‐pQCT) scans to measure Ct.Po and Ct.Th and use it to compare Ct.Po and Ct.Th between pre‐ and postmenopausal women with normal, osteopenic, and osteoporotic areal bone mineral density (aBMD). The Ct.Po and Ct.Th measurements were validated using cadaver forearms (n = 10) and micro‐computed tomography (µCT) as the gold standard. The analysis was applied to distal radius and tibia HR‐pQCT scans from a subset of participants from the Calgary, Alberta, cohort of the Canadian Multicentre Osteoporosis Study (n = 280, 18 to 90 years). Analysis of covariance compared Ct.Po and Ct.Th outcomes between 63 normal premenopausal (dual‐energy X‐ray absorptiometry femoral neck T‐score > ?1), 87 normal postmenopausal, 121 osteopenic postmenopausal, and 9 osteoporotic postmenopausal women. Linear regression analysis and Bland‐Altman plots were used to assess the agreement between the HR‐pQCT and µCT measurements, resulting in r² values of 0.80 for Ct.Po and 0.98 for Ct.Th. At both sites, Ct.Po was higher in postmenopausal (all groups) than in premenopausal women (3.2% to 12.9%, p < .001). Ct.Th was not significantly different between normal premenopausal and postmenopausal women at either site; however, both osteopenic and osteoporotic women had thinner (?12.8% to ?30.3%, p < .01), more porous (2.1% to 8.1%, p < .001) cortices than normal postmenopausal women. Our method offers promise as a valuable tool to measure Ct.Po and Ct.Th in vivo and investigate associations among cortical bone structure, age, and disease status. © 2010 American Society for Bone and Mineral Research.     

Early impairment of trabecular microarchitecture assessed with HR‐pQCT in patients with stage II‐IV chronic kidney disease

Bone fragility is a complication of chronic kidney disease (CKD). The aim of this study was to assess whether volumetric bone mineral density (vBMD) and microarchitecture could be impaired early in the course of CKD. Bone microarchitecture was examined with a noninvasive 3D imaging technique [high‐resolution peripheral quantitative computed tomography (HR‐pQCT)] at the tibia and radius in 70 stage II‐IV CKD patients older than 50 years of age; controls belonged to two cohorts of healthy subjects comparable for age and gender (OFELY cohort in women and STRAMBO cohort in men). We examined 46 men and 24 women; 19 patients were diabetic. Mean age was 70.8 ± 8.5 years, mean glomerular filtration rate (GFR) was 34 ± 12 mL/min per 1.73 m², and mean serum parathyroid hormone (PTH) level was 87 ± 59 pg/mL. Both CKD men and women experienced a moderate but significant trabecular (Tb) impairment, positioning CKD patient values between those of normal and osteopenic controls (e.g., CKD men versus healthy controls: Tb vBMD 172 ± 35 versus 188 ± 34 mg HA/cm³; Tb number 1.75 ± 0.27 versus 1.86 ± 0.26 mm^?1, and Tb separation 503 ± 94 versus 465 ± 78 µm; p < .05). Cortical thickness (Ct.Th) in men also was significantly decreased compared with healthy controls (e.g., CKD men versus healthy controls: tibial Ct.Th 1171 ± 331 versus 1288 ± 283 µm; p < .05). In conclusion, this study, using a noninvasive bone‐imaging device, shows for the first time an early impairment of trabecular microarchitecture in stage II‐IV CKD patients. Further longitudinal studies should be performed to validate HR‐pQCT as a tool for predicting the fracture risk in CKD. © 2010 American Society for Bone and Mineral Research.     

A comparison of bone quality at the distal radius between Asian and white adolescents and young adults: An HR‐pQCT study

Paradoxically, Asians have lower areal bone mineral density (aBMD), but their rates of hip and wrist fractures are lower than whites. Therefore, we used high‐resolution pQCT (HR‐pQCT) to determine whether differences in bone macrostructure and microstructure, BMD, and bone strength at the distal radius were apparent in Asian (n = 91, 53 males, 38 females, [mean ± SD] 17.3 ± 1.5 years) and white (n = 89, 46 males, 43 females, 18.1 ± 1.8 years) adolescents and young adults. HR‐pQCT outcomes included total BMD (Tt.BMD), trabecular bone volume fraction (BV/TV), and trabecular number (Tb.N), thickness (Tb.Th), and separation (Tb.Sp). We used an automated segmentation algorithm to determine total bone area (Tt.Ar), and cortical BMD (Ct.BMD), porosity (Ct.Po), and thickness (Ct.Th), and we applied finite element (FE) analysis to HR‐pQCT scans to estimate bone strength. We fit sex‐specific multivariable regression models to compare bone outcomes between Asians and whites, adjusting for age, age at menarche (girls), lean mass, ulnar length, dietary calcium intake, and physical activity. In males, after adjusting for covariates, Asians had 11% greater Tt.BMD, 8% greater Ct.BMD, and 25% lower Ct.Po than whites (p < 0.05). Also, Asians had 9% smaller Tt.Ar and 27% greater Ct.Th (p < 0.01). In females, Asians had smaller Tt.Ar than whites (16%, p < 0.001), but this difference was not significant after adjusting for covariates. Asian females had 5% greater Ct.BMD, 12% greater Ct.Th, and 11% lower Tb.Sp than whites after adjusting for covariates (p < 0.05). Estimated bone strength did not differ between Asian and white males or females. Our study supports the notion of compensatory elements of bone structure that sustain bone strength; smaller bones as observed between those of Asian origin compared with white origin have, on average, more dense, less porous, and thicker cortices. Longitudinal studies are needed to determine whether ethnic differences in bone structure exist in childhood, persist into old age, and whether they influence fracture risk.     

Physical Activity,Sedentary Time,and Bone Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR‐pQCT study

Bone strength is influenced by bone geometry, density, and bone microarchitecture, which adapt to increased mechanical loads during growth. Physical activity (PA) is essential for optimal bone strength accrual; however, less is known about how sedentary time influences bone strength and its determinants. Thus, our aim was to investigate the prospective associations between PA, sedentary time, and bone strength and its determinants during adolescence. We used HR‐pQCT at distal tibia (8% site) and radius (7% site) in 173 girls and 136 boys (aged 9 to 20 years at baseline). We conducted a maximum of four annual measurements at the tibia (n = 785 observations) and radius (n = 582 observations). We assessed moderate‐to‐vigorous PA (MVPA) and sedentary time with accelerometers (ActiGraph GT1M). We aligned participants on maturity (years from age at peak height velocity) and fit a mixed‐effects model adjusting for maturity, sex, ethnicity, leg muscle power, lean mass, limb length, dietary calcium, and MVPA in sedentary time models. MVPA was a positive independent predictor of bone strength (failure load [F.Load]) and bone volume fraction (BV/TV) at the tibia and radius, total area (Tt.Ar) and cortical porosity (Ct.Po) at the tibia, and negative predictor of load‐to‐strength ratio at the radius. Sedentary time was a negative independent predictor of Tt.Ar at both sites and Ct.Po at the tibia and a positive predictor of cortical thickness (Ct.Th), trabecular thickness (Tb.Th), and cortical bone mineral density (Ct.BMD) at the tibia. Bone parameters demonstrated maturity‐specific associations with MVPA and sedentary time, whereby associations were strongest during early and mid‐puberty. Our findings support the importance of PA for bone strength accrual and its determinants across adolescent growth and provide new evidence of a detrimental association of sedentary time with bone geometry but positive associations with microarchitecture. This study highlights maturity‐specific relationships of bone strength and its determinants with loading and unloading. Future studies should evaluate the dose‐response relationship and whether associations persist into adulthood. © 2017 American Society for Bone and Mineral Research.     

Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Adult Patients With Hypophosphatemic Rickets

Hypophosphatemic rickets (HR) is characterized by a generalized mineralization defect. Although densitometric studies have found the patients to have an elevated bone mineral density (BMD), data on bone geometry and microstructure are scarce. The aim of this cross‐sectional in vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated bone strength in adult patients with HR using high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Twenty‐nine patients (aged 19 to 79 years; 21 female, 8 male patients), 26 of whom had genetically proven X‐linked HR, were matched with respect to age and sex with 29 healthy subjects. Eleven patients were currently receiving therapy with calcitriol and phosphate for a median duration of 29.1 years (12.0 to 43.0 years). Because of the disproportionate short stature in HR, the region of interest in HR‐pQCT images at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age‐ and weight‐adjusted models, HR patients had significantly higher total bone cross‐sectional areas (radius 36%, tibia 20%; both p < 0.001) with significantly higher trabecular bone areas (radius 49%, tibia 14%; both p < 0.001) compared with controls. In addition, HR patients had lower total vBMD (radius ?20%, tibia ?14%; both p < 0.01), cortical vBMD (radius ?5%, p < 0.001), trabecular number (radius ?13%, tibia ?14%; both p < 0.01), and cortical thickness (radius ?19%; p < 0.01) compared with controls, whereas trabecular spacing (radius 18%, tibia 23%; p < 0.01) and trabecular network inhomogeneity (radius 29%, tibia 40%; both p < 0.01) were higher. Estimated bone strength was similar between the groups. In conclusion, in patients with HR, the negative impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter, resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research.     

Bone Density,Microstructure and Strength in Obese and Normal Weight Men and Women in Younger and Older Adulthood

Obesity is associated with greater areal BMD (aBMD) and is considered protective against hip and vertebral fracture. Despite this, there is a higher prevalence of lower leg and proximal humerus fracture in obesity. We aimed to determine if there are site‐specific differences in BMD, bone structure, or bone strength between obese and normal‐weight adults. We studied 100 individually‐matched pairs of normal (body mass index [BMI] 18.5 to 24.9 kg/m²) and obese (BMI >30 kg/m²) men and women, aged 25 to 40 years or 55 to 75 years. We assessed aBMD at the whole body (WB), hip (TH), and lumbar spine (LS) with dual‐energy X‐ray absorptiometry (DXA), LS trabecular volumetric BMD (Tb.vBMD) by quantitative computed tomography (QCT), and vBMD and microarchitecture and strength at the distal radius and tibia with high‐resolution peripheral QCT (HR‐pQCT) and micro–finite element analysis. Serum type 1 procollagen N‐terminal peptide (P1NP) and collagen type 1 C‐telopeptide (CTX) were measured by automated electrochemiluminescent immunoassay (ECLIA). Obese adults had greater WB, LS, and TH aBMD than normal adults. The effect of obesity on LS and WB aBMD was greater in older than younger adults (p < 0.01). Obese adults had greater vBMD than normal adults at the tibia (p < 0.001 both ages) and radius (p < 0.001 older group), thicker cortices, higher cortical BMD and tissue mineral density, lower cortical porosity, higher trabecular BMD, and higher trabecular number than normal adults. There was no difference in bone size between obese and normal adults. Obese adults had greater estimated failure load at the radius (p < 0.05) and tibia (p < 0.01). Differences in HR‐pQCT measurements between obese and normal adults were seen more consistently in the older than the younger group. Bone turnover markers were lower in obese than in normal adults. Greater BMD in obesity is not an artifact of DXA measurement. Obese adults have higher BMD, thicker and denser cortices, and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest that obesity may protect against age‐related bone loss and may increase peak bone mass. © 2014 American Society for Bone and Mineral Research.     

Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Klinefelter Syndrome

Although the expected skeletal manifestations of testosterone deficiency in Klinefelter's syndrome (KS) are osteopenia and osteoporosis, the structural basis for this is unclear. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in patients with KS. Thirty‐one patients with KS confirmed by lymphocyte chromosome karyotyping aged 35.8 ± 8.2 years were recruited consecutively from a KS outpatient clinic and matched with respect to age and height with 31 healthy subjects aged 35.9 ± 8.2 years. Dual‐energy X‐ray absorptiometry (DXA) and HR‐pQCT were performed in all participants, and blood samples were analyzed for hormonal status and bone biomarkers in KS patients. Twenty‐one KS patients were on long‐term testosterone‐replacement therapy. In weight‐adjusted models, HR‐pQCT revealed a significantly lower cortical area (p < 0.01), total and trabecular vBMD (p = 0.02 and p = 0.04), trabecular bone volume fraction (p = 0.04), trabecular number (p = 0.05), and estimates of bone strength, whereas trabecular spacing was higher (p = 0.03) at the tibia in KS patients. In addition, cortical thickness was significantly reduced, both at the radius and tibia (both p < 0.01). There were no significant differences in indices of bone structure, estimated bone strength, or bone biomarkers in KS patients with and without testosterone therapy. This study showed that KS patients had lower total vBMD and a compromised trabecular compartment with a reduced trabecular density and bone volume fraction at the tibia. The compromised trabecular network integrity attributable to a lower trabecular number with relative preservation of trabecular thickness is similar to the picture found in women with aging. KS patients also displayed a reduced cortical area and thickness at the tibia, which in combination with the trabecular deficits, compromised estimated bone strength at this site. © 2014 American Society for Bone and Mineral Research.     

Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures

Measurement of areal bone mineral density (aBMD) by dual‐energy x‐ray absorptiometry (DXA) has been shown to predict fracture risk. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR‐pQCT. Finite‐element analysis (FEA) of HR‐pQCT scans was performed to estimate bone stiffness. DXA T‐scores were similar in women with and without fracture at the spine, hip, and one‐third radius but lower in patients with fracture at the ultradistal radius (p < .01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p < .0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p < .0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p < .01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR‐pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility. © 2010 American Society for Bone and Mineral Research.     

Relationships between bone geometry,volumetric bone mineral density and bone microarchitecture of the distal radius and tibia with alcohol consumption

PurposeChronic heavy alcohol consumption is associated with bone density loss and increased fracture risk, while low levels of alcohol consumption have been reported as beneficial in some studies. However, studies relating alcohol consumption to bone geometry, volumetric bone mineral density (vBMD) and bone microarchitecture, as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), are lacking.MethodsHere we report an analysis from the Hertfordshire Cohort Study, in which we studied associations between HR-pQCT measures at the distal radius and tibia and alcohol consumption in 376 participants (198 men and 178 women) aged 72.1–81.4 years.ResultsA total of 30 (15.2%), 90 (45.5%) and 78 (39.4%) men drank minimal/none (< 1 unit/week), low (≥ 1 unit/week and < 11 units/week) and moderate/high (≥ 11 units/week) amounts of alcohol respectively. These figures were 74 (41.8%), 80 (45.2%) and 23 (13.0%) respectively in women for minimal/none (< 1 unit/week), low (≥ 1 unit/week and < 8 units/week) and moderate/high (≥ 8 units/week). At the distal radius, after adjustment for confounding factors (age, BMI, smoking status, dietary calcium intake, physical activity and socioeconomic status and years since menopause and HRT use for women), men that drank low alcohol had lower cortical thickness (p = 0.038), cortical vBMD (p = 0.033), and trabecular vBMD (p = 0.028) and higher trabecular separation (p = 0.043) than those that drank none/minimal alcohol. Similar differences were shown between minimal/none and moderate/high alcohol although these only reached statistical significance for the cortical parameters. Interestingly, after similar adjustment, women showed similar differences in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia. However, women that drank moderate/high alcohol had significantly higher trabecular vBMD (p = 0.007), trabecular thickness (p = 0.026), and trabecular number (p = 0.042) and higher trabecular separation (p = 0.026) at the distal radius than those that drank low alcohol.ConclusionsOur results suggest that alcohol consumption (low and moderate/high) may have a detrimental impact on bone health in men in both the cortical and trabecular compartments at the distal radius with similar results in women in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia suggesting that avoidance of alcohol may be beneficial for bone health.     

Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Adult Patients With Type 1 Diabetes Mellitus

The primary goal of this cross‐sectional in vivo study was to assess peripheral bone microarchitecture, bone strength, and bone remodeling in adult type 1 diabetes (T1D) patients with and without diabetic microvascular disease (MVD+ and MVD–, respectively) and to compare them with age‐, gender‐, and height‐matched healthy control subjects (CoMVD+ and CoMVD–, respectively). The secondary goal was to assess differences in MVD– and MVD+ patients. Fifty‐five patients with T1DM (MVD+ group: n = 29) were recruited from the Funen Diabetes Database. Dual‐energy X‐ray absorptiometry (DXA), high‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the ultradistal radius and tibia, and biochemical markers of bone turnover were performed in all participants. There were no significant differences in HR‐pQCT parameters between MVD– and CoMVD– subjects. In contrast, MVD+ patients had larger total and trabecular bone areas (p = 0.04 and p = 0.02, respectively), lower total, trabecular, and cortical volumetric bone mineral density (vBMD) (p < 0.01, p < 0.04, and p < 0.02, respectively), and thinner cortex (p = 0.03) at the radius, and lower total and trabecular vBMD (p = 0.01 and p = 0.02, respectively) at the tibia in comparison to CoMVD+. MVD+ patients also exhibited lower total and trabecular vBMD (radius p = 0.01, tibia p < 0.01), trabecular thickness (radius p = 0.01), estimated bone strength, and greater trabecular separation (radius p = 0.01, tibia p < 0.01) and network inhomogeneity (radius p = 0.01, tibia p < 0.01) in comparison to MVD– patients. These differences remained significant after adjustment for age, body mass index, gender, disease duration, and glycemic control (average glycated hemoglobin over the previous 3 years). Although biochemical markers of bone turnover were significantly lower in MVD+ and MVD– groups in comparison to controls, they were similar between the MVD+ and MVD– groups. The results of our study suggest that the presence of MVD was associated with deficits in cortical and trabecular bone vBMD and microarchitecture that could partly explain the excess skeletal fragility observed in these patients. © 2015 American Society for Bone and Mineral Research.     

Levels of serotonin,sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high‐bone‐mass phenotype due to a mutation in Lrp5

Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment‐specific changes in bone. The relationship between the phenotype and serum serotonin is not well documented. To evaluate bone, serotonin, and bone turnover markers (BTM) in Lrp5‐HBM patients, we studied 19 Lrp5‐HBM patients (T253I) and 19 age‐ and sex‐matched controls. DXA and HR‐pQCT were used to assess BMD and bone structure. Serum serotonin, sclerostin, dickkopf‐related protein 1 (DKK1), and BTM were evaluated. Z‐scores for the forearm, total hip, lumbar spine, forearm, and whole body were significantly increased (mean ± SD) between 4.94 ± 1.45 and 7.52 ± 1.99 in cases versus ?0.19 ± 1.19 to 0.58 ± 0.84 in controls. Tibial and radial cortical areas, thicknesses, and BMD were significantly higher in cases. In cases, BMD at the lumbar spine and forearm and cortical thickness were positively associated and trabecular area negatively associated with age (r = 0.49, 0.57, 0.74, and ?0.61, respectively, p < .05). Serotonin was lowest in cases (69.5 [29.9–110.4] ng/mL versus 119.4 [62.3–231.0] ng/mL, p < .001) and inversely associated with tibial cortical density (r = ?0.49, p < .05) and directly with osteocalcin (OC), bone‐specific alkaline phosphatase (B‐ALP), and procollagen type 1 amino‐terminal propeptide (PINP) (r = 0.52–0.65, p < .05) in controls only. OC and S‐CTX were lower and sclerostin higher in cases, whereas B‐ALP, PINP, tartrate‐resistant acid phosphatase (TRAP), and dickkopf‐related protein 1 (DKK1) were similar in cases and controls. In conclusion, increased bone mass in Lrp5‐HBM patients seems to be caused primarily by changes in trabecular and cortical bone mass and structure. The phenotype appeared to progress with age, but BTM did not suggest increased bone formation. © 2011 American Society for Bone and Mineral Research     

Sex Differences and Growth‐Related Adaptations in Bone Microarchitecture,Geometry, Density,and Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR‐pQCT Study

Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR‐pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post‐APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post‐APHV at the tibia when girls’ values were 2% greater than boys’. Boys showed 13% to 48% greater cortical and total bone area across growth. Load‐to‐strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR‐pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys’ superior bone size and strength compared with girls may confer them a protective advantage. However, boys’ consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR‐pQCT that target boys and girls who have sustained a fracture are needed to verify this. © 2016 American Society for Bone and Mineral Research.