Spine Bone Mineral Density Measurements Research Articles

Impact of Adding Distal Forearm Bone Mineral Density Measurement to Axial Bone Mineral Density Measurement for the Diagnosis of Osteoporosis: Prevalence and Risk Factors for Diagnostic Discordance

Background: Studies have demonstrated the superiority of distal forearm bone mineral density (BMD) measurement over axial BMD measurement for prediction of osteoporotic fractures of distal radius. However, distal forearm BMD measurement is not routinely performed at most centers. Objective: To demonstrate the prevalence of discordance in diagnosis of osteoporosis using axial and distal forearm BMD measurement, and to assess whether age and other potential risk factors can predict major discordance. Materials and Methods: Postmenopausal women aged 45 years or older and men aged 50 years or older who underwent lumbar spine, hip, and distal forearm BMD measurement at Prompt Health Center, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand, between January 2021 and December 2021 were recruited. The T-scores of axial site and distal forearm were categorized based on World Health Organization classification to determine the prevalence of diagnostic discordance. Major discordance was defined as having one osteoporotic and one normal T-score. Factors potentially associated with major discordance were explored using univariate and multivariate logistic regression models. Results: Eight hundred eighty-one participants including 621 women and 260 men with a mean age of 59.2±6.7 years were analyzed. There were 13.2% participants diagnosed with osteoporosis of the axial site, and 16.0% of the one-third (1/3) radius. The rates of major discordance, minor discordance, and concordance between axial and 1/3 radius T-scores were 3.2%, 40.5%, and 56.3%, respectively. Age of 65 years or older was significantly associated with major axial and 1/3 radius T-score discordance, with an adjusted odds ratio of 2.7 and 95% confidence interval 1.24 to 5.87 (p=0.012). Conclusion: Diagnostic discordance is observed for at least one-third of the participants using axial and distal forearm BMD measurement. The age of 65 years or older is a risk factor for major discordance. Keywords: Bone mineral density; Osteoporosis; Spine; Hip; Distal forearm; Discordance

Problematic video gaming is negatively associated with bone mineral density in adolescents.

Adolescent bone health may be negatively impacted by problematic video gaming (PVG) due to factors such as prolonged screen time, poor sleep quality, and increased depression. Although sedentary behaviors have been linked to decreased bone mass, there is limited research on how PVG impacts bone health. We aimed to evaluate the association between PVG and bone mineral density (BMD) in adolescents by comparing the BMD z-scores of adolescents with and without PVG and by identifying PVG-related risk factors that may affect low BMD scores. This cross-sectional study took place between May 2019 and August 2021 with 110 adolescents who played video games for at least two hours per day. Data on screen time, game genre, tobacco, alcohol, caffeine consumption, and vigorous physical activity status were recorded. PVG was assessed using the Internet Gaming Disorder-Short Form (IGDS9-SF), with scores ≤ 16 comprising the control group and > 16 the PVG group. Sleep quality was assessed by Pittsburgh Sleep Quality Index, and depression was evaluated by Children's Depression Inventory. Dual-energy X-ray absorptiometry measurements of femoral neck and lumbar spine BMD were compared between the two groups. The mean age of the participants was 14.2 ± 1.8years, and 86.4% were males. The PVG group exhibited lower femoral neck z-scores (p = 0.013) and a higher proportion of adolescents with low femoral neck BMD risk (27.8% vs 9.7%, p = 0.041). Lumber spine z-scores did not differ (p = 0.271). Despite poorer depressive symptoms and sleep quality in the PVG group, they were not associated with low BMD risk (OR 1.02, 95% CI 0.97-1.08, p = 0.398 and OR 1.00, 95% CI 0.87-1.18, p = 0.972, respectively). Among all PVG-related risk factors, video game time (aOR = 1.22, 95% CI = 1.06-1.41, p = 0.006) and vigorous physical activity amount (aOR = 2.86, 95% CI = 0.93-8.76, p = 0.080) showed the strongest associations with femoral neck z-scores. Conclusion: The results of this study, showing a negative association between PVG and femoral neck BMD in adolescents, underscore the importance evaluating, monitoring, and supporting lower extremity bone health in adolescents with PVG. What is Known: • Adolescents with problematic video gaming are at risk for depression, impaired sleep; sedentary lifestyle; consumption of tobacco, alcohol, and drugs; and high caffeine intake. • These risk factors might lead to compromised bone health. What is New: • Problematic video gaming is associated with the low femoral neck bone mineral density risk in adolescents. • Extended video game time and reduced physical activity are found to be the primary risk factors.

Effects of Severe Lumbar Spine Structural Artifact on Trabecular Bone Score (TBS): The Manitoba BMD Registry

Trabecular bone score (TBS) is a bone mineral density (BMD)-independent risk factor for fracture. During DXA analysis and BMD reporting, it is standard practice to exclude lumbar vertebral levels affected by structural artifact. Although TBS is relatively insensitive to degenerative artifact, it is uncertain whether TBS is still useful in the presence extreme structural artifact that precludes reliable spine BMD measurement even after vertebral exclusions. Among individuals aged 40 years and older undergoing baseline DXA assessment from September 2012 to March 2018 we identified three mutually exclusive groups: spine BMD reporting performed without exclusions (Group 1, N=12,865), spine BMD reporting performed with vertebral exclusions (Group 2, N=4867), and spine BMD reporting not performed due to severe structural artifact (Group 3, N=1541). No significant TBS difference was seen for Group 2 versus Group 1 (referent), whereas TBS was significantly greater in Group 3 (+0.041 partially adjusted, +0.043 fully adjusted). When analyzed by the reason for vertebral exclusion, multilevel degenerative changes significantly increased TBS (+0.041 partially adjusted, +0.042 fully adjusted), while instrumentation significantly reduced TBS (-0.059 partially adjusted, -0.051 fully adjusted). Similar results were seen when analyses were restricted to those in Group 3 with a single reason for vertebral exclusions, and when follow up scans were also included. During mean follow-up of 2.5 years there were 802 (4.2 %) individuals with one or more incident fractures. L1-L4 TBS showed significant fracture risk stratification in all groups including Group 3 (P-interaction >0.4). In conclusion, lumbar spine TBS can be reliably measured in the majority of lumbar spine DXA scans, including those with artifact affecting up to two vertebral levels. However, TBS is significantly affected by the presence of extreme structural artifact in the lumbar spine, especially those with multilevel degenerative disc changes and/or instrumentation that precludes reliable BMD reporting.

The choice of region of interest after spinal procedures alters bone mineral density measurements.

Vertebrae affected by artifacts, such as metallic implants or bone cement, should be excluded when measuring the spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Exclusion may be performed using two methods: first, the affected vertebrae are included in the region of interest (ROI) and subsequently excluded from the analysis; second, the affected vertebrae are completely excluded from the ROI. This study aimed to investigate the influence of metallic implants and bone cement on BMD with and without the inclusion of artifact-affected vertebrae in the ROI. DXA images of 285 patients, including 144 with spinal metallic implants and 141 who had undergone spinal vertebroplasty from 2018 to 2021, were retrospectively reviewed. Spine BMD measurements were performed when the images were evaluated using two different ROIs for each patient during the same examination. In the first measurement, the affected vertebrae were included in the ROI; however, the affected vertebrae were excluded from the BMD analysis. In the second measurement, the affected vertebrae were excluded from the ROI. Differences between the two measurements were evaluated using a paired t-test. Among 285 patients (average age, 73 years; 218 women), spinal metallic implants led to an overestimation of bone mass in 40 of 144 patients, whereas bone cement resulted in an underestimation of bone mass in 30 of 141 patients when the first measurement was compared with the second measurement. The opposite effect occurred in 5 and 7 patients, respectively. Differences in results between the inclusion and exclusion of the affected vertebrae in the ROI were statistically significant (p<0.001). Spinal implants or cemented vertebrae included in the ROI might significantly alter BMD measurements. Additionally, different materials were associated with varying modifications in BMD. The inclusion of affected vertebrae in the ROI may notably alter BMD measurements, even when they are excluded from the analysis. This study suggests that the vertebrae affected by spinal metallic implants or bone cement should be excluded from the ROI.

The Effect of General Bone Mineral Density on the Quantity and Quality of the Edentulous Mandible: A Cross-Sectional Clinical Study

Osteoporosis is a disease which is characterized by a decrease in general bone mineral density (BMD), resulting in decreased bone strength and an increased risk of bone fractures. The effect of reduced BMD on the jawbones is still not fully understood. The purpose of the study was to evaluate the impact of BMD on the quality and quantity of the edentulous mandible. The present study included 127 edentulous postmenopausal women who underwent cone beam computed tomography (CBCT) examinations. BMD measurements of the lumbar spine and femoral necks were performed by dual-energy X-ray absorptiometry. In the cross-sectional CBCT images, three different areas of the mandible (lateral incisor, first premolar, and first molar) were selected. The complete mandibular, trabecular, and cortical bone volumes were measured. All measurements were performed on the total mandibular area, and the basal and alveolar parts of the mandible. The volume of the cortical bone was reduced for females with reduced BMD in the lateral incisor and first premolar regions, both in the total mandibular area and in the basal part of the mandible. The trabecular bone volume statistically significantly increased when the BMD decreased in the complete mandibular area and the basal part of the mandible (linear regression). The total bone volume significantly decreased with a decrease in BMD in the basal part of the mandible. Reduced BMD has a negative effect on the quantity and quality of bone in the basal part of the edentulous mandible.

Prevalence and Risk Factors of Discordance Between Hip and Spinal Bone Mineral Density Among Saudi Subjects.

BackgroundDiscordance between hip and spine on dual-energy x-ray absorptiometry is a well-known problem in diagnosing osteoporosis. The prevalence and risk factors of this problem have not been studied in the Saudi population. The objective of this study was to document this discordance in our population and its possible risk factors.Materials and methodsWe analyzed data obtained from subjects who had dual x-ray absorptiometry (DXA) between January 2021 and December 2021 at King Khalid University Hospital, Riyadh, Saudi Arabia. Subjects with the following conditions were excluded: secondary osteoporosis, patients taking anti-osteoporotic agents, patients on steroids or hormonal replacement therapy, hyperparathyroidism, hypoparathyroidism, and chronic renal disease. A total of 1388 patients satisfied our inclusion criteria. World Health Organization (WHO) criteria for diagnosis were implemented. Major discordance was defined as osteoporosis in one site and normal in the other. Minor discordance was defined as a difference of no more than one World Health Organization diagnostic class between two sites. Bivariate statistical analysis was achieved using appropriate statistical tests (chi-square, student’s t-test, one-way analysis of variance, and Pearson’s correlation), based on the type of study and outcome variables. A p-value of < 0.05 and 95% CI were used to report the statistical significance and precision of results.ResultsA total of 1388 subjects were analyzed, of which, 1196 (86%) were females with a mean age of 58.8 (13.8 SD) and 192 were males with a mean age of 58 (18.0 SD). Lumbar osteoporosis was found in 312 (22.5%) participants while hip osteoporosis was reported in 73 (5.3%) of the participants. Major discordance was documented in 85 (6.1%) of all participants (6.3% of the male and 6.1% of the female patients). All of these subjects had lumbar spine osteoporosis with normal hip bone mineral density (BMD). Minor discordance was found in 591 patients (42.6%). Obesity (BMI > 30) was found to be a risk factor for both major (2.10-11.6, 95% CI) and minor (2.5-11.4, 95% CI) discordance.ConclusionDiscordance between hip and spine BMD is common among Saudi subjects. Lumbar spine osteoporosis with normal hip BMD caused this discordance in our subjects. Obesity could be responsible for the occurrence of this discordance. Mechanisms may include higher rate of turnover in spine, technical artifacts in the measurements of lumbar spine BMD, or due to the effects of weight loading. Caution should be exercised when interpreting DXA results, especially in obese subjects.

Lumbar Spine Bone Mineral Density Measurement: Comparison of Dual-Energy X-Ray Absorptiometry and Fat Content Evaluation by Dixon Chemical Shift MRI.

BackgroundTo assess whether the fat signal intensity and fat fraction (FF) of the lumbar vertebrae as measured on the Dixon chemical shift magnetic resonance imaging (MRI) technique can be correlated with the lumbar vertebra bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA).MethodsForty-five patients were retrospectively collected, and 180 lumbar vertebral bodies (L1-L4) were included. All patients underwent DXA and MRI examinations of the lumbar spine. Taking the T value of DXA as the gold standard and using the diagnostic criteria of the World Health Organization: T score ≥ −1.0SD as normal, −1.0 ~ −2.5SD as osteopenia, and ≤ −2.5SD as osteoporosis. Meanwhile, the signal intensity on T2WI was measured, and FF of L1-L4 vertebral bodies was calculated on MRI images. Bone marrow fat FF calculation formula: FF = [Mfat/(Mfat + Mwater)] × 100% (Mwater and Mfat refer to the total pixel signal intensity value of the region of interest in water image and lipid image, respectively). Finally, the association of signal intensity and FF with DXA was evaluated.ResultsTotally 180 vertebral bodies in 45 patients were enrolled. According to the T value, they were divided into the normal group (n = 70), osteopenia group (n = 40), and osteoporosis group (n = 70). The fat signal intensity of the normal group, osteopenia group, and osteoporosis group were 96.6 ± 21.8, 154.5 ± 48.7, 216.3 ± 92.6, and the FF were 30.1 ± 6.2%, 52.6 ± 7.6%, 77.5 ± 7.9%, respectively. Among the three groups, the lumbar T2 fat signal intensity and FF had statistical differences (P < 0.01). Besides, the lumbar fat signal intensity and FF were negatively related to DXA (r =−0.65 and −0.93, P < 0.01).ConclusionThe fat content calculated using the Dixon chemical shift MRI had an inverse relation with BMD. Moreover, the Dixon chemical shift MRI might provide complementary information to osteoporosis-related research fields.

Is the skull responsive to bone mineralisation stimuli in children?

Whole-body-less-head (WBLH) is the recommended skeletal region of interest (ROI) for dual-energy X-ray absorptiometry (DXA) assessment of bone mineral density (BMD) in children. Historically it has been suggested that the skull is less responsive than the rest of the skeleton to stimuli that affect BMD but there are few published data to support this notion. We compared the associations of BMD with anthropometric, body composition, diet, and activity variables across various ROI. Children from the Southampton Women's Survey (SWS) mother-offspring cohort participated at age 6-7years, including measurement of height, weight, and whole-body and lumbar spine (LS) BMD by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart) and diet by interviewer-led questionnaire. BMD was measured in the following skeletal ROI: whole-body, skull, WBLH and lower limbs (all derived from the whole-body scan) and LS. 1218 children participated. Height z-score, weight z-score, lean mass and milk intake were associated with skull BMD, but associations were weaker than observed for other ROI; for example, the association between lean mass and skull BMD was β (95% CI) 0.11 (0.08, 0.14) SD/kg, compared with 0.32 (0.30, 0.34), 0.38 (0.37, 0.40) and 0.23 (0.21, 0.25) SD/kg for whole body, WBLH and lumbar spine, respectively. Relationships with whole-body BMD were attenuated compared with WBLH. Associations between skull BMD and anthropometry, body composition and dietary variables were weaker than for other DXA sites. These findings support, and importantly provide a quantitative basis for, the recommendation that the skull should be excluded from whole-body DXA analyses in children.

Trabecular Bone Score and Osteoprotegerin as Useful Tools in the Assessment of Bone Deterioration in Acromegaly.

PurposeThis study aimed to assess bone mineral density (BMD) and trabecular bone score (TBS) in 61 patients from the acromegaly group (AG) with regard to the activity of the disease in comparison to 42 patients—control group (CG). We also analyzed selected bone markers and their association with BMD and TBS.Materials and MethodsLumbar spine and femoral neck BMD measurements were performed. TBS values were obtained. Serum concentrations of selected bone markers, including osteoprotegerin (OPG), were measured.ResultsWe revealed a difference in TBS values between the AG and CG as well as between the TCA (treatment-controlled acromegaly) vs. CG and TCA+CA (cured acromegaly) vs. CG. We did not observe any statistically significant difference in BMD. OPG had a lower concentration in the CG compared to the AG. TBS correlated negatively with OPG in the AG (r = −0.31, p = 0.01) and in the TCA+ CA group (r = −0.3, p = 0.01).ConclusionsThe acromegalic patients have altered bone microstructure as indicated by the decreased TBS regardless of the activity of the disease and BMD. OPG could be a marker of the destruction of the bone microstructure, but further studies are needed.

Bone mineral density and vitamin D levels in parkinson’s disease: A retrospective controlled study

Aim: This study aimed to compare bone mineral density and vitamin D levels in patients with Parkinson’s Disease (PD) and healthy controls.Methods: Eighty-six patients aged 60-85, diagnosed with PD and receiving regular medical treatment for the disease were screened. Data for 34 participants (19 women and 15 men) meeting the inclusion criteria were entered into the retrospective analysis. The data for 31 healthy age- and sex-matched participants (18 women and 13 men) were also included. Bone mineral density (BMD) values and vitamin D levels of each participant were recorded.Results: BMD values for the femoral neck and total hip in the PD group were statistically significantly lower than healthy controls. In addition, T-scores for the femoral neck, total hip, and trochanteric area, and Z-scores for the total hip and trochanteric area were also lower in the patients with PD than in the healthy controls. The two groups did not have significant differences regarding lumbar spinal BMD measurements and T- and Z-score values or vitamin D levels.Conclusion: PD’s total hip and femoral neck BMD measurements are low. Further multicenter studies involving larger patient populations are now needed to understand the incidence and mechanisms of osteoporosis in PD.

The Effect of Dietary Protein and Amino Acid Intake on Total Hip and Lumbar Spine Bone Mineral Density Measurements

The Effect of Dietary Protein and Amino Acid Intake on Total Hip and Lumbar Spine Bone Mineral Density Measurements

Gray values of the cervical vertebrae detected by cone beam computed tomography for the identification of osteoporosis and osteopenia in postmenopausal women

This study aimed to determine whether the gray values (GVs) of the second and third cervical vertebrae in cone beam computed tomography (CBCT) are affected by general bone mineral density (BMD) in postmenopausal women and to evaluate whether CBCT can be used for predicting the risk of osteoporosis. The present cross-sectional study included 127 edentulous postmenopausal women (average age, 70.4 ± 8.9 years) who underwent CBCT examinations. BMD measurements of the lumbar spine and both femoral necks were performed by dual-energy x-ray absorptiometry. The CBCT images were analyzed with OnDemand3D Dental software. GVs of the axial and sagittal sections of the cervical second and third vertebral bodies were obtained. The GVs of the second and third cervical vertebrae decreased significantly with decreasing BMD. The axial GV of the second cervical vertebra showed the highest sensitivity (80.6%), highest negative predictive value (89.0%), lowest negative likelihood ratio (0.39), and highest area under the curve value (0.68) to predict osteoporosis. Women with reduced BMD have lower GVs for the second and third cervical vertebrae. Changes in the GV of the second vertebra can potentially be used to determine the risk of osteoporosis in postmenopausal women.

Distal radial cortical bone thickness correlates with bone mineral density and can predict osteoporosis: a cohort study

PurposeThe purpose of this study was to evaluate the correlation of the bone mineral density (BMD) of the hip and lumbar spine with the distal radius cortical thickness (DRCT) measured on anteroposterior radiographs and establish a method for predicting osteoporosis. MethodsWe assessed 147 patients aged ≥50 years with distal radius fractures who underwent wrist radiographs and dual-energy X-ray absorptiometry. The DRCT was measured and calculated at two levels of the distal radius of the injured wrist on the radiographs. ResultsThe intra-rater and inter-rater reliability of measures was excellent (intraclass correlation coefficient >0.85). In the Pearson correlation and simple linear regression analyses, the DRCT was positively correlated with hip BMD (r = 0.393, P < 0.01) and lumbar spine BMD (r = 0.529, P < 0.01). Each 1-mm increase in DRCT was associated with a 0.051-g/cm2 increase in hip BMD (R2 = 0.154, P < 0.01) and a 0.080-g/cm2 increase in lumbar spine BMD (R2 = 0.280, P < 0.01). A DRCT of 5.1 mm was selected as the cutoff point for predicting osteoporosis, with the highest Youden index of 0.560, 83.3% sensitivity, 72.7% specificity, and a 66.7% negative predictive value. ConclusionCortical thickness measurements obtained from anteroposterior wrist radiographs were positively correlated with hip and lumbar spine BMD measurements. This technique is suggested as a rapid, inexpensive, and sensitive method for predicting osteoporosis. Level of evidenceDiagnostic II

Infant milk feeding and bone health in later life: findings from the Hertfordshire cohort study.

Using data from the Hertfordshire cohort study (HCS), this study aims to examine the effect of infant milk feeding on bone health in later life by comparing the effect of breastfeeding and bottle feeding on lumbar spine and femoral neck BMC and BMD. Information about infant milk feeding, birth weight (kg) and weight at 1 (kg) was collected by health visitors between 1931 and 1939 in Hertfordshire. BMC and BMD measurements were taken by DXA scan between 1998 and 2004. Linear regression models adjusted for conditional weight at 1, age at DXA scan, sex, adult BMI, smoking behaviour, alcohol consumption, physical activity, dietary calcium, and prudent diet score. Infant milk feeding was significantly associated with lumbar spine BMD (b = - 0.028; 95% CI, - 0.055; - 0.000; p value, 0.047) in males. On average, males who consumed breastmilk alternatives in infancy had lower lumbar spine BMD measurements than those who were fed only breastmilk. These associations remained significant in fully adjusted models. There were no significant associations between infant milk feeding and bone health for females. Significant associations between infant milk feeding and lumbar spine BMD in males indicate that breastmilk may be protective for the bone health of male babies. The evidence presented here underscores the potential lifelong benefits of breastfeeding and may highlight the differences between osteoporotic risk factors for males and females.

Assessment of Agreement of Wrist Bone Mineral Density with Spine and Hip Bone Mineral Density in Postmenopausal Women

Objective: Worldwide, osteoporosis in postmenopausal women is a common public health problem. The measurement of bone mineral density (BMD) of spine and hip using central dual energy X-ray absorptiometry (DXA) is the most standard technique to diagnose osteoporosis. But in many circumstances, measurement of spine or hip BMD is quite difficult to carry out where wrist BMD can be used as an alternative. Moreover, wrist BMD can be done with smaller, cheaper, portable peripheral devices for screening osteoporosis at primary health care level. The objective of the study was to explore the agreement of wrist BMD with spine and hip BMD in postmenopausal women.&#x0D; Patients and Methods: This observational, cross sectional study was carried out at National Institute of Nuclear Medicine &amp; Allied Sciences (NINMAS), Bangabandhu Sheikh Mujib Medical University (BSMMU) campus, from July 2017 to June 2018. A total of 110 postmenopausal women referred to NINMAS for BMD measurement were enrolled in this study after fulfilling selection criteria. BMD of spine, right and left hip and wrist of enrolled subjects were measured by dual energy X-ray absorptiometry (DXA) scan by Stratos DR Bone densitometer.&#x0D; Results: Agreement analysis done by kappa statistics revealed kappa value of 0.930 (p&lt;0.05), 0.782 (p&lt;0.05) and 0.635 (p&lt;0.05) between wrist and spine BMD, wrist and right hip BMD and wrist and left hip BMD, respectively. In Bland-Altman analysis, the mean difference of T-score measured by wrist and spine was -0.007 ± 1.361, wrist and right hip was -0.645 ± 1.271 and wrist and left hip was -0.450 ± 1.259 with 95% of differences were found in between -2.674 and 2.660, -3.136 and 1.846 and -2.917 and 2.017, respectively. Positive significant Pearson’s correlation was observed between wrist BMD and spine BMD (r=0.664; p=0.001), wrist BMD and right hip BMD (r=0.719; p=0.001) and wrist BMD and left hip BMD (r=0.727; p=0.001).&#x0D; Conclusion: This study results showed an excellent kappa agreement between wrist and spine BMD with good kappa agreement of wrist with right and left hip BMD as well as in Bland-Altman analysis, the mean differences of T-score between wrist andspine, wrist and right hip and wrist and left hip were small. The biases between the methods were considered not significant suggesting that these sites can be used interchangeably for measurement of BMD. Hence, wrist BMD can be used with regular skeletal sites (spine and hip) as an effective method of diagnosing osteopenia and osteoporosis by DXA where spine or hip BMD is difficult to carry out as well as it can be used for osteoporosis screening at primary health care level by portable peripheral DXA device to initiate early treatment to reduce fracture risks.&#x0D; Bangladesh J. Nuclear Med. 22(1): 41-46, Jan 2019

Standard Versus Cyclic Teriparatide and Denosumab Treatment for Osteoporosis: A Randomized Trial.

In the absence of an intervening antiresorptive agent, cyclic administration of teriparatide does not increase bone mineral density (BMD) more than standard daily therapy. Because denosumab is a potent antiresorptive agent with a rapid off-effect, we hypothesized that it might be the optimal agent to help maximize bone gains with cyclic teriparatide. In this 3-year protocol, 70 postmenopausal women with osteoporosis were randomized to 18 months of teriparatide followed by 18 months of denosumab (standard) or three separate 12-month cycles of 6 months of teriparatide followed by 6 months of denosumab (cyclic). BMD (dual-energy X-ray absorptiometry [DXA]) measurements of lumbar spine (LS), total hip (TH), femoral neck (FN), and 1/3 radius (RAD) were performed every 6 months and total body bone mineral (TBBM) at 18 and 36 months. Baseline descriptive characteristics did not differ between groups except for a minimal difference in LS BMD but not T-score (mean age 65 years, mean LS T-score - 2.7). In the standard group, BMD increments at 36 months were: LS 16%, TH 4%, FN 3%, and TBBM 4.8% (all p < 0.001 versus baseline). In the cyclic group, 36-month BMD increments were similar: LS 12%, TH 4%, FN 4%, and TBBM 4.1% (all p < 0.001 versus baseline). At 36 months, the LS BMD increase with standard was slightly larger than with cyclic (p = 0.04), but at 18 months, in the cyclic group, there was no decline in RAD or TBBM (p = 0.007 and < 0.001, respectively, versus standard). Although the cyclic regimen did not improve BMD compared with standard at 36 months, there appeared to be a benefit at 18 months, especially in the highly cortical skeletal sites. This could be clinically relevant in patients at high imminent risk of fracture, particularly at nonvertebral sites. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Influence of Thyroid-stimulating Hormone Suppression Therapy on Bone Mineral Density in Patients with Differentiated Thyroid Cancer: A Meta-analysis.

BackgroundThe effects of subclinical hyperthyroidism on bone mineral density (BMD) induced by thyroid-stimulating hormone (TSH) suppression therapy in patients with differentiated thyroid cancer (DTC) remains unclear. We conducted a meta-analysis to determine the influence of TSH suppression therapy on BMD.MethodsWe performed a systematic search to identify studies which included BMD measurement of femoral neck, total hip or lumbar spine in patients on TSH suppression therapy for DTC. Main outcome measures were difference of BMD of femoral neck, total hip or lumbar spine measured by dual energy X-ray absorptiometry between patients and controls.ResultsA systematic search yielded a total of 11 published controlled cross-sectional studies (including about 571 patients and 836 controls). TSH suppression therapy was associated with the lower BMD of total hip (weighted mean difference [WMD], −0.023; 95% confidence interval [CI], −0.047 to 0.000; P=0.050) and spine (WMD, −0.041; 95% CI, −0.057 to −0.026; P<0.001) in postmenopausal women with DTC, while it was not associated with that in premenopausal women and men with DTC.ConclusionsAlthough the included studies were limited by small numbers, results suggested possible association between chronic TSH suppression therapy and the lower BMD of spine and total hip in postmenopausal women (but not in premenopausal women and men) with DTC. A large, well-designed study with long-term follow-up would provide further insight into the influence of TSH suppression therapy and loss of BMD.

Potential association with early changes in serum calcium level after starting or switching to denosumab combined with eldecalcitol.

The aims of this study are to investigate changes in serum calcium (Ca) level after switching from either non-therapy, bisphosphonate, selective estrogen receptor modulators (SERM) or teriparatide treatments to a combination therapy of denosumab (DMAb), and eldecalcitol, and the association between early changes in serum calcium and changes in bone metabolic markers and bone mineral density (BMD). 129 patients with postmenopausal osteoporosis (32 non-pretreatment, 50 bisphosphonates, 18 SERM, and 29 teriparatide) were recruited and switched to DMAb plus eldecalcitol. Serum calcium levels, bone metabolism markers, and BMD measurements of the lumbar spine and femoral neck were evaluated. All groups showed an increase in BMD 6months and 1year after DMAb administration compared to baseline via suppression of bone metabolism markers. The TPD group showed a significant decrease in serum calcium level 1week after the first injection of DMAb and eldecalcitol compared to baseline and the bisphosphonate group. Changes in serum calcium level from baseline to 1week after the first injection of DMAb trended to correlate with changes in bone metabolism markers and lumbar BMD. The risks of DMAb-induced hypocalcemia are different between starting and switching from bone resorption inhibitors and bone formation promoters. Therefore, appropriate assessment before administration of DMAb, including pretreatment therapy as well as serum Ca and bone metabolic markers will help identify the risk of hypocalcemia following DMAb in combination with eldecalcitol. Our findings also showed that early change in serum Ca level after DMAb initiation could potentially predict the efficacy for therapy reaction.

Low trabecular bone score in adolescent female inpatients with anorexia nervosa

Trabecular bone score (TBS) is an emerging technology that provides information regarding bone microarchitecture. A recent study showed that in healthy girls normal TBS (≥1.35) was achieved within the first year post-menarche. The aims of our study was to assess TBS in adolescents with anorexia nervosa (AN) and to evaluate correlations with clinical, laboratory and densitometric variables. A cohort study of 208 adolescent females (mean age 15.6±1.8y) hospitalized because of AN between 2003 and 2017 was retrospectively assessed. Demographic and clinical data, including age, weight, height, body mass index (BMI), laboratory parameters and bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA) were retrieved from the medical charts. Bone mineral apparent density (BMAD) was calculated for each participant. TBS was assessed by reanalyzing DXA spinal images. Mean TBS was 1.308±0.083, lower than the values previously described in healthy adolescents (p<0.001). Compromised microarchitecture was found in 17 participants (8.2%) and partially compromised in 123 (59.1%). TBS was significantly correlated with age, weight standard deviation score (SDS), BMI SDS, BMD measurements of the lumbar spine and total body, BMAD, BMAD Z-score, luteinizing hormone (LH) and 17b-estradiol (E2) level, and was negatively correlated with cortisol (p=0.017). Participants with regular menstruation or secondary amenorrhea had higher TBS than participants who were pre-menarche or with primary amenorrhea (p<0.001). A stepwise linear regression analysis identified BMD L1-4 Z-score and log E2 as independent predictors of TBS. TBS of adolescent females with AN was found to be lower than TBS of healthy adolescents. Prospective longitudinal studies should be undertaken to investigate whether recovery may result in correction of bone microarchitecture.

Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study

Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis and is associated with an estimated annual fracture rate of 5%. We aimed to assess the efficacy and safety of denosumab compared with risedronate in glucocorticoid-induced osteoporosis. We did a 24-month, double-blind, active-controlled, double-dummy, non-inferiority study at 79 centres in Europe, Latin America, Asia, and North America. Eligible patients were aged 18 years or older and were receiving glucocorticoids (≥7·5 mg prednisone daily, or equivalent) for at least 3 months (glucocorticoid continuing) or less than 3 months (glucocorticoid initiating) before screening. Patients younger than 50 years needed to have a history of osteoporosis-related fracture; glucocorticoid-continuing patients aged 50 years or older needed a lumbar spine, total hip, or femoral neck bone mineral density T score of -2·0 or less, or -1·0 or less if they had a history of osteoporosis-related fracture. Participants were randomly assigned (1:1) to either 60 mg subcutaneous denosumab every 6 months and oral placebo daily for 24 months, or 5 mg oral risedronate daily and subcutaneous placebo every 6 months for 24 months. Randomisation was stratified by sex within each subpopulation, and was done with an interactive voice-response system. Active drugs and corresponding placebos had identical packaging, labels, and appearance. The primary outcome was non-inferiority of denosumab to risedronate in terms of percentage change from baseline in lumbar spine bone mineral density at 12 months based on non-inferiority margins (-0·7 and -1·1 percentage points for the glucocorticoid-continuing and glucocorticoid-initiating subpopulations, respectively). Superiority was also assessed as a secondary outcome. The primary efficacy set included all randomly assigned participants who had a baseline and postbaseline lumbar spine bone mineral density measurement, and was analysed according to randomised treatment assignment. The safety analysis set included all randomly assigned participants who received at least one dose of investigational product, and was analysed by actual treatment received. This study is registered with ClinicalTrials.gov (NCT01575873) and is completed. Between March 28, 2012, and June 30, 2015, 795 patients, 505 of whom were glucocorticoid continuing and 290 of whom were glucocorticoid initiating, were enrolled and randomly assigned (398 to denosumab, 397 to risedronate). Denosumab was both non-inferior and superior to risedronate at 12 months for effect on bone mineral density at the lumbar spine in both glucocorticoid-continuing (4·4% [95% CI 3·8-5·0] vs 2·3% [1·7-2·9]; p<0·0001) and glucocorticoid-initiating (3·8% [3·1-4·5] vs 0·8% [0·2-1·5]; p<0·0001) subpopulations. Incidence of adverse events, serious adverse events (including infections), and fractures was similar between treatment groups. The most common adverse events were back pain (17 [4%] patients in the risedronate group and 18 [5%] in the denosumab group) and arthralgia (21 [5%] patients in the risedronate group and 17 [4%] in the denosumab group). Serious infection occurred in 15 (4%) patients in the risedronate group and 17 (4%) patients in the denosumab group. Denosumab could be a useful treatment option for patients newly initiating or continuing glucocorticoids who are at risk of fractures. Amgen.