Opportunistic Evaluation of Bone Mineral Density By Pet-Ct in Hodgkin Lymphoma Patients

Objective: Bone density loss and increased risk for osteoporosis are of concern in Hodgkin lymphoma (HL) patients. Routinely performed positron emission tomography–computed tomography (PET-CT) scans could be informative in assessing bone mineral density (BMD).Methods: This retrospective study included 80 adults with newly diagnosed HL treated with standard first-line chemotherapy regimens. PET-CT scans performed at diagnosis (PET-CT₁), at the end of chemotherapy (PET-CT₂), and at follow-up after remission (PET-CT₃) were used to assess BMD changes by measuring lumbar vertebrae CT attenuation. A CT attenuation threshold of 160 Hounsfield units was used to define abnormal BMD.Results: Following chemotherapy, comparison of PET-CT₂ with PET-CT₁ revealed a mean (standard deviation) 14.2% (10.4%) BMD reduction (P<.001). On PET-CT₃ performed at 14.6 (3.25) months after the last course of chemotherapy, a slight improvement (4.6% &lsqb;10.4%]) in comparison to PET-CT₂ was noted. Twelve patients (15%) converted from normal baseline BMD on PET-CT₁ to abnormal BMD after chemotherapy on PET-CT₂. Age, baseline BMD, and steroid cumulative dose were associated with BMD decline and risk for abnormal BMD after chemotherapy. No clinical fractures were reported, and only one rib fracture was incidentally captured (1.25%).Conclusion: HL patients treated with common first-line chemotherapies demonstrate a significant decline in bone density on routine PET-CT scans. Opportunistic use of PET-CT scan has the potential to detect HL patients at high risk for developing osteoporosis and to guide clinicians regarding monitoring and intervention.Abbreviations: BMD = bone mineral density; CT = computed tomography; DXA = dual-energy X-ray absorptiometry; HL = Hodgkin lymphoma; HU = Hounsfield units; L = lumbarvertebra; PET-CT = positron emission tomography-computed tomography; T = thoracic vertebra     

Dual-Energy X-Ray Absorptiometry And Calculated Frax Risk Scores May Underestimate Osteoporotic Fracture Risk In Vitamin D-Deficient Veterans With Hiv Infection

Objective: We evaluated the utility of the Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency.Methods: This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures.Results: We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between -1 and -2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant.Conclusion: We found a high prevalence of subclinical vertebral fractures among vitamin D–deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population.Abbreviations:25(OH)D = 25-hydroxyvitamin DBMD = bone mineral densityBMI = body mass indexDEXA = dual-energy X-ray absorptiometryFRAX = Fracture Risk Assessment ToolHIV = human immunodeficiency virusIQR = interquartile rangePTH = parathyroid hormoneVA = Veterans AffairsWHO = World Health Organization     

Influence of cardiovascular disease risk factors on the relationship between low bone mineral density and type 2 diabetes mellitus in a multiethnic us population of women and men: A cross-sectional study

Introduction: Higher bone mineral density (BMD) has been reported among white women and men with type 2 diabetes mellitus (DM) compared with nondiabetic white individuals, but there is scant evidence for nonwhite persons. It is also not known whether cardiovascular disease (CVD) risk factors may confound any association between BMD and type 2 DM.Objective: The present study examined the relationship between low BMD and type 2 DM in a multiethnic population of women and men while controlling for the influence of osteoporosis and CVD risk factors including body mass index (BMI), cigarette smoking, physical inactivity, total cholesterol and its components, blood pressure, and C-reactive protein.Methods: Data collected from 4929 African American, Mexican American, and white women and men aged 50 to 79 years who participated in the household interview and clinical examinations during the Third National Health and Nutrition Examination Survey were analyzed. CVD risk factors associated with type 2 DM in this study population were included as covariates in gender-specific multiple logistic regression models assessing the relationship between type 2 DM and low BMD while controlling for osteoporosis risk factors. Gender- and race/ethnicity-specific mean BMD values at the total hip for young adults aged 20 to 29 years were used to establish race/ethnicity and gender-specific low BMD T-scores.Results: The final study population included 2505 women and 2424 men. More women and men with type 2 DM than women and men without type 2 DM were nonwhite and had high BMI. Osteoporosis risk factors but not CVD risk factors were associated with low BMD in both women and men. Type 2 DM was not associated with low BMD among women (odds ratio [OR] = 0.77; 95% CI, 0.56-1.08). Based on a statistically significant interaction between type 2 DM status and race/ethnicity, white men with type 2 DM were less likely to have low BMD than were white men without type 2 DM (OR = 0.56; 95% CI, 0.37-0.86; P = 0.01). There was no significant BMD difference between diabetic and nondiabetic nonwhite men.Conclusion: CVD risk factors did not appear to influence the relationship between low BMD and type 2 DM in this study     

Effects of Bisphosphonates on Osteoporosis Induced by Duchenne Muscular Dystrophy: A Prospective Study

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD.Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated.Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group (P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline).Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol.Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid     

The Risk of Bone Fractures in Post-Poliomyelitis Patients Transitioning to Middle Adulthood

ObjectiveWhile osteoporotic fractures are reported in up to 40% of adults with post-poliomyelitis syndrome (PPS), clinical guidelines regarding bone mineral density (BMD) and indications for treatment are scarce. We investigated the characteristics of PPS patients, focusing on fractures and osteoporosis as the primary outcomes.MethodsA cross-sectional retrospective data analysis from medical records of 204 PPS patients regarding their clinical characteristics and long-term outcome, with emphasis on bone metabolism status.ResultsOur cohort included 53% women; mean age was 65 years at study entry and 1.7 years at the diagnosis of acute poliomyelitis. The lower limb was involved in 97.5% of patients, and the BMD in the affected limb tended to be lower than the unaffected, with a mean T-score of -1.64 vs. -1.19, respectively (P = .06). Recurrent falls were documented in 39.2% of patients, and osteoporosis in 20.6%, being more frequent in women (P = .003) and patients with fractures (P = .002). At least one fracture occurred in 52.2% of patients, and more than one in 40.3%. The median age for the first fracture was 57.5 years (range, 30 to 83 years), and most fractures occurred in the affected limb (73.2%).ConclusionsUnderdiagnosis and delayed treatment of osteoporosis in late-adulthood post-poliomyelitis patients underlie the need for comprehensive clinical guidelines to manage these patients, including recommendations on bone health assessment, medical treatment, and their inclusion as a high-risk group for bone fractures.     

Anabolic Therapy and Optimal Treatment Sequences for Patients With Osteoporosis at High Risk for Fracture

Objective: Provide an update regarding anabolic medications for osteoporosis, which are often considered to be the last resort for patients with osteoporosis, after multiple fractures have already occurred and other medications have already been administered.Methods: Literature review and discussion.Results: Recent pivotal trial data for anabolic agents and randomized trials comparing anabolic and antiresorptive medications suggest that three anabolic agents (teriparatide, abaloparatide, and romosozumab) reduce nonvertebral and vertebral fractures faster and to a greater extent than potent antiresorptive treatments. Furthermore, bone density accrual is maximized when patients are given anabolic agents first, followed by potent antiresorptive therapy. Since total hip bone density during or after osteoporosis treatment has emerged as an excellent surrogate for future fracture risk, attaining a greater hip bone mineral density is a treatment goal for high-risk osteoporosis patients.Conclusion: This review defines the highest-risk patients and summarizes the rationale for the evolving role of anabolic therapy in the management of postmenopausal women at high risk for fracture.Abbreviations: ACTIVE = Abaloparatide Comparator Trial in Vertebral Endpoints; ARCH = Active Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; BMD = bone mineral density; FRAME = Fracture Study in Postmenopausal Women with Osteoporosis; FRAX = Fracture Risk Assessment Tool; PTH = parathyroid hormone; TBS = trabecular bone score     

Exposure to Famine in Early Life and the Risk of Osteoporosis in Adulthood: a Prospective Study

Objective: To assess the association between famine exposure in early life and osteoporosis in adulthood.Methods: A total of 2,292 participants born between 1955 and 1965 in Fujian Province were selected; after 3 years, 1,378 participants attended a follow-up research visit. Calcaneus bone mineral density and bone quality were measured by quantitative ultrasound. The T-score was used to assess bone mineral density, and the parameters quantitative ultrasound index (QUI), speed of sound (SOS), and broadband ultrasonic attenuation (BUA) were used to assess bone quality. A T-score threshold of -1.8 was defined as osteoporosis, and a possible vertebral fracture was considered as a prospective height loss of 0.8 inches or more.Results: Compared with the nonexposed cohort, risks of osteoporosis for fetal-, early childhood, and mid-childhood famine-exposed cohorts in postmenopausal women were adjusted odds ratio (OR), 3.741 (95% confidence interval [CI], 1.233, 11.44) versus OR 2.894 (95% CI, 0.997, 8.571) versus OR 4.699 (95% CI, 1.622, 13.612) by logistic regression but not significant in men. Moreover, the fetal-exposed cohort had a weak negative relation with QUI (β, -5.07 [-10.226, 0.127]) and BUA (β, -4.321 [-0.88, 0.238]). The early- and mid-childhood–exposed cohorts had significantly lower QUI (β, -7.085 [-11.799, -2.372] versus β, -10.845 [-15.68, -6.01]) and BUA (β, -6.381 [-10.515, -2.246] versus β, -8.573 [-12.815, -4.331]) than the nonexposed cohort by linear regression. None of the famine-exposed cohorts had a significant relationship with SOS.Conclusion: Famine exposure during early life is associated with higher risk of osteoporosis in adulthood, which is most obvious in postmenopausal women. Furthermore, famine exposure in early life has adverse effects on bone quality.Abbreviations: BMD = bone mineral density; BUA = broadband ultrasonic attenuation; CI = confidence interval; OR = odds ratio; QUI = quantitative ultrasound index; QUS = quantitative ultrasound; SOS = speed of sound     

Frax Prediction without BMD for Assessment of Osteoporotic Fracture Risk

ObjectiveTo compare Fracture Risk Assessment Tool (FRAX) calculations with and without bone mineral density (BMD) in predicting the 10-year probability of hip and major osteoporotic fractures (MOF).MethodsA cross-sectional review of patients requiring screening for osteoporosis as part of their routine medical care was conducted. Postmenopausal women and men over 50 years of age who were never diagnosed with osteoporosis or treated with U.S. Food and Drug Administration-approved agents for osteoporosis were included. Height, weight, FRAX questionnaire, femoral neck BMD, and T-score data were obtained. FRAX scores with BMD (FRAX/BMD) and without BMD (FRAX) were calculated. Subjects were separated on the basis of identical and different treatment recommendations. Fracture risk factors were compared between groups using simple Student’s t test analysis of numerical variables and Fisher’s exact test analysis of binary variables.ResultsOf 151 total subjects, 127 (84%) had identical fracture risk predictions with or without BMD included in the FRAX calculation. Thirty subjects met treatment criteria and 97 did not, but the FRAX prediction was the same with risk factors alone or with risk factors plus BMD. Age was the only risk factor that was significantly different between those with identical and different predictions (median age, 64.42 and 76.25 years, respectively; P&#x003C;.001).ConclusionIn most cases, FRAX alone provides the same prediction as FRAX with BMD. Younger age is more indicative of an identical prediction. (Endocr Pract. 2013;19:780-784)     

Osteoporotic Fractures During Bisphosphonate Drug Holiday

Objective: Bisphosphonate (BP) drug holidays are recommended to lower the risk of rare adverse events, such as atypical femoral fractures and osteonecrosis of the jaw. However, there are minimal data on the optimal duration of these holidays. Our aim was to determine the clinical and laboratory parameters associated with increased fracture risk in patients on BP drug holiday.Methods: A retrospective chart review was conducted of 401 patients with osteopenia or osteoporosis who began a BP drug holiday from 2004 to 2013. Collected parameters included demographics, prior therapy, bone mineral density (BMD), bone turnover markers, parathyroid hormone, calcium & vitamin D status, and clinical reports of fractures.Results: Sixty-two (15.4%) patients developed a fracture during follow-up. The yearly incidence of fractures ranged from 3.7 to 9.9%, peaking at 9.9% and 9.8% during years 4 and 5, respectively. The mean age of the fracture group was higher than the nonfracture group, though not significantly different (69.24 ± 12.26 years vs. 66.42 ± 10.18 years; P = .09). Compared to the nonfracture group, the fracture group had lower femoral neck BMD (0.75 ± 0.12 g/cm² vs. 0.79 ± 0.10 g/cm²; P = .03) and T-scores (-2.13 ± 0.99 vs. -1.78 ± 0.79; P = .01) at baseline.Conclusion: Patients who begin BP drug holidays at high risk of fracture based on BMD, age, or other clinical risk factors warrant close follow-up, especially as its duration lengthens. Fracture risk analysis needs to be regularly assessed during the drug holiday and treatment resumed accordingly.Abbreviations:25-OHD = 25-hydroxyvitamin DAACE = American Association of Clinical EndocrinologistsACE = American College of EndocrinologyBMD = bone mineral densityBP = bisphosphonateBSAP = bone-specific alkaline phosphataseBTM = bone turnover markerFN = femoral neckLS = lumbar spinePTH = parathyroid hormone     

Trabecular Bone Score Change Differs with Regard to 25(OH)D Levels in Patients Treated for Adult-Onset Growth Hormone Deficiency

Objective: Vitamin D is important in bone health. However, potential relationships of concomitant vitamin D deficiency with growth hormone deficiency (GHD) and the possibility that vitamin D inadequacy may alter the skeletal effects of growth hormone (GH) replacement therapy have not been adequately evaluated.Methods: A prospective study was conducted in adult-onset GHD patients treated with recombinant human GH (rhGH) for 2 years. Trabecular bone score (TBS), lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and 25-hydroxyvitamin D (25(OH)D) levels were assessed at baseline and 24 months. The study cohort was divided based on 25(OH)D levels into 2 groups with the cutoff defined as the 50^th percentile at each follow-up time point.Results: Fifty-seven patients (29 males/28 females, mean age 34.4 years) were studied. After 24 months of GH replacement, LS BMD increased by 7.6% and TH BMD increased by 4.5% (both P<.05), with no difference according to 25(OH)D levels. TBS increased (+1.39 ± 3.6%) in those whose 25(OH)D was above the 50^th percentile but decreased (-1.36 ± 5.6%, P<.05) in the cohort below the 50^th percentile of 25(OH)D. Positive correlations were observed between baseline levels of IGF-1 and 25(OH)D (R = 0.37, P<.001) and between 24-month 25(OH)D and TBS (R = 0.25, P<.05).Conclusion: A differential effect of GH on TBS change was observed; TBS increased only in the cohort with 25(OH)D above the 50^th percentile. Vitamin D sufficiency may be required to obtain optimal effects of GH treatment on bone quality, as assessed by TBS, in GHD adults.Abbreviations:AO-GHD = adult-onset GHDBMD = bone mineral densityBMI = body mass indexCa = calciumCTx = carboxyterminal collagen crosslinksCV = coefficient of variationDXA = dual energy X-ray absorptiometryECLIA = enzyme-labeled chemiluminescent immunometric assayGH = growth hormoneGHD = growth hormone deficiencyIGF-1 = insulin-like growth factor 1LS BMD = lumbar spine BMDOC = osteocalcin25(OH)D = 25-hydroxyvitamin DP = phosphorusPTH = parathyroid hormonerhGH = recombinant human GHTBS = trabecular bone scoreTH BMD = total hip BMD     

Correlation Between Bone Markers and Bone Mineral Density in Postmenopausal Women with Osteoporosis

ObjectiveTo study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.MethodsEighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Patients with low serum vitamin D levels, secondary osteoporosis, or clinically significant systemic disease were excluded from the study. The patients were classified on the basis of BMD of the lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through -3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score ≤-4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < .05 being considered significant.ResultsSerum osteocalcin was significantly different among the 3 study groups (4.1 ± 2.7, 4.5 ± 3.1, and 6.7 ± 5.6 ng/mL, respectively; P = .0349) and had a significant negative correlation with BMD (r² = -0.0779; P = .0168). Other bone markers such as bone-specific alkaline phosphatase and urinary free deoxypyridinoline did not correlate with the underlying BMD.ConclusionIn our study, osteocalcin was significantly correlated with BMD in postmenopausal women with osteoporosis. Other bone markers did not correlate with BMD. Further large-scale population data and analyses are needed to confirm these findings. (Endocr Pract. 2008;14:1102-1107)     

Comparison Of The Long-Term Effects Of Liraglutide And Glimepiride Monotherapy On Bone Mineral Density In Patients With Type 2 Diabetes

Objective: Patients with type 2 diabetes have an increased risk of fragility fractures; the cause is unclear but is likely multifactorial. Some diabetes treatments induce bone loss, accentuating underlying skeletal fragility and increasing fracture risk. This subgroup analysis aimed to compare long-term effects of liraglutide and glimepiride on bone mineral density (BMD) in patients with type 2 diabetes.Methods: LEAD-3, a 52-week, double-blind, activecontrol, phase III, multicenter trial, investigated the efficacy of liraglutide (1.2 and 1.8 mg/day) versus glimepiride monotherapy in type 2 diabetes. A 52-week, open-label extension followed, in which participants remained on randomized therapy. A subgroup of participants underwent BMD measurement by dual-energy X-ray absorptiometry at baseline, 52, and 104 weeks. The main outcome measure was change from baseline in total body BMD at 52 and 104 weeks, assessed by analysis of covariance.Results: A total of 746 patients with type 2 diabetes aged 19 to 79 years were randomized into the main trial. Of these, 61 patients (20 assigned to liraglutide 1.8 mg/day, 23 to liraglutide 1.2 mg/day, 18 to glimepiride 8 mg/day) had BMD measurements. Baseline age, body mass index, diabetes duration, glycated hemoglobin, and total BMD were similar across treatment groups. There was no apparent difference in mean total BMD change from baseline in patients receiving liraglutide 1.8 or 1.2 mg/day or glimepiride 8 mg/day at 52 or 104 weeks.Conclusion: In this small subgroup analysis, liraglutide monotherapy did not negatively affect total BMD in a 2-year prospective study, suggesting it may not exacerbate the consequences of bone fragility.Abbreviations:BMD = bone mineral densityBMI = body mass indexDPP-4 = dipeptidyl peptidase-4DXA = dual-energy X-ray absorptiometryGLP-1RA = glucagon-like peptide 1 receptor agonistLEAD = Liraglutide Effect and Action in DiabetesTZD = thiazolidinedione     

Prevalence of Osteoporosis in Ambulatory Postmenopausal Women from A Semiurban Region in Southern India: Relationship to Calcium Nutrition and Vitamin D Status

ObjectiveTo assess the prevalence of osteoporosis in healthy ambulatory postmenopausal Indian women as measured by dual-energy x-ray absorptiometry and to study the dietary calcium intake and vitamin D status and their influence on bone mineral density (BMD).MethodsWe conducted a community-based crosssectional study in a semiurban region. A randomized cluster sampling technique was used. The study cohort consisted of 150 ambulatory postmenopausal women (≥ 50 years old). Dual-energy x-ray absorptiometry for BMD was performed at the lumbar spine and femoral neck. Dietary calcium intake and biochemical variables were assessed.ResultsThe prevalence of osteoporosis was 48% at the lumbar spine, 16.7% at the femoral neck, and 50% at any site. The mean dietary calcium intake was much lower than the recommended intake for this age-group. There was a significant positive correlation between body mass index and BMD at the lumbar spine and the femoral neck (r = 0.4; P = .0001). BMD at the femoral neck was significantly less (mean, 0.657 versus 0.694 g/cm²) in the vitamin D-insufficient study subjects in comparison with the vitamin D-sufficient women (P = .03).ConclusionThe high prevalence of osteoporosis and vitamin D insufficiency in this semiurban group of postmenopausal women in India is a major health concern. Measures such as adequate calcium intake and vitamin D supplementation in women of this age-group may be beneficial. (Endocr Pract. 2008;14:665-671)     

Bone Mineral Density In Patients With Addison Disease On Replacement Therapy With Prednisolone

Objective: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement.Methods: Forty-one consecutive patients (31 males, age &lsqb;mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent &lsqb;HCE] 13.0 ± 3.0 mg/m²) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677).Results: Among males, BMD Z-scores (mean &lsqb;95% confidence interval {CI}]) at lumbar spine (-0.42 &lsqb;-0.80, -0.04]), femoral neck (-0.50 &lsqb;-0.95, -0.06]) and total hip (-0.58 &lsqb;-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD.Conclusions: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.Abbreviations:ACTH = adrenocorticotropic hormoneBAP = bone-specific alkaline phosphataseBMD = bone mineral densityBMI = body mass indexCI = confidence intervalHCE = hydrocortisone equivalent25 (OH) D3 = 25-hydroxyvitamin D3PAI = primary adrenal insufficiency     

The Effects of Hyponatremia on Bone Density and Fractures: A Systematic Review and Meta-Analysis

Objective: Hyponatremia decreases bone mineral density and is a major risk factor for fragility fractures. Objectives of our systematic review and meta-analysis were to analyze the overall effects of hyponatremia on bone fractures, osteoporosis, and mortality.Methods: We extracted data from Medline, Cochrane Central, and EMBASE 1960–2017 and conference abstracts from 2007–2017. We included studies with data on serum sodium, fractures, bone density, or diagnoses of osteoporosis. Studies were independently reviewed by two authors and assessed for bias using the Newcastle-Ottawa scale. Random effect models meta-analysis was used when at least three studies reported the same outcome measures. We reported summary odds ratios (ORs) and 95% confidence intervals (CIs).Results: We included 26 studies for qualitative analysis. Fifteen studies were included in the meta-analysis to evaluate the effects of hyponatremia on fractures, four studies for bone mineral density changes, and six for mortality. Hyponatremia increased the odds of fractures at all sites (summary OR, 2.34 [95% CI, 1.86, 2.96]. There was an increase in the odds of osteoporosis (summary OR, 2.67 [95% CI, 2.07, 3.43]). Mortality risk among the included studies remained high (summary OR, 1.31 [95% CI, 1.16, 1.47]).Conclusion: Our meta-analysis confirms a statistically significant association of hyponatremia with bone fractures and osteoporosis along with higher mortality. Long-term prospective studies evaluating the impact of correcting hyponatremia on bone health, fractures, and mortality are required.Abbreviations: AVP = arginine vasopressin; CI = confidence interval; CKD = chronic kidney disease; OR = odds ratio; SIADH = syndrome of inappropriate antidiuretic hormone     

The Clinical Characteristics and Efficacy of Bisphosphonates in Audlt Patients with Osteogenesis Impergecta

Objective: Osteogenesis imperfecta (OI) is characterized by low bone mass and recurrent fractures. Adults with OI are often treated with oral or intravenous bisphosphonates (BPs). We investigated the clinical phenotypes of adult OI patients and prospectively compared the efficacy of oral alendronate (ALN) with intravenous zoledronic acid (ZOL) in OI patients.Methods: This 24-month, observational, randomized clinical study included 60 adult patients with OI. We compared the differences in bone mineral density (BMD) and bone turnover biomarkers between OI adults and healthy subjects. Thereafter, OI patients were randomized at a 2:1 ratio to receive either weekly oral ALN 70 mg or once-yearly infusion of ZOL 5 mg. The efficacy outcomes were changes in BMD, bone turnover biomarkers, and fracture incidence.Results: Adult OI patients had significantly lower BMD and significantly higher cross-linked C-telopeptide of type I collagen (β-CTX) levels than age-/sex-/BMI-matched healthy subjects. A total of 52 patients completed the 24-month clinical study. BMD at lumbar spine, femoral neck, and total hip were equivalently elevated in the ALN (10.5, 13.2, and 14.7%, respectively) and ZOL (11.3, 13.7, and 11.7%, respectively; all P>.05) groups. Serum alkaline phosphatase decreased by 30.3% in the ALN group and 37.3% in the ZOL group (P =.12), and β-CTX decreased by 58.0% in the ALN group and 63.6% in the ZOL group (P =.48). Compared to the prior fracture rates, clinical fracture incidences were decreased in the ALN and ZOL groups (both P<.05).Conclusion: Adults with OI present significantly lower bone mass and higher bone resorption biomarkers than healthy populations. Oral ALN and intravenous ZOL are equally effective at increasing BMD and inhibiting bone turnover in adults with OI. The treatment may reduce fractures in this study, but further efforts are still needed to demonstrate the anti-fracture efficacy of BPs.Abbreviations:25OHD = 25-hydroxyvitamin DALN = alendronateALP = alkaline phosphataseBMD = bone mineral densityBMI = body mass indexBP = bisphosphonateβ-CTX = cross-linked C-telopeptide of type I collagenFN = femoral neckLS = lumbar spineOI = osteogenesis imperfectaRCT = randomized controlled trialTH = total hipZOL = zoledronic acid     

Adding VFA to DXA Identifies Fracture Risk in a Way Not Duplicated by Other Measures

Objective: Published studies have demonstrated that adding vertebral fracture assessment (VFA) to dual-energy X-ray absorptiometry (DXA) identifies more patients with increased fracture risk than DXA alone. But who needs VFA? This study attempts to determine if some test other than VFA could duplicate the additional information obtained by performing VFA on all first-time patients. This study looked at the Fracture Risk Assessment Tool (FRAX), height loss, age, documented back pain, and nonvertebral fragility fractures.Methods: VFA was performed on 1,259 (all) DXA patients at their first visit from March 2010 through September 2013. All DXA and VFA results were read by the same International Society for Clinical Densitometry–certified clinician.Results: By DXA alone, 44% were osteoporosis. Adding VFA increased clinical osteoporosis by 36% of the original total patients. Eighty-three “normal bone mineral density” patients were changed to clinical osteoporosis. FRAX identified 53% of the patients with diagnosis changes. Historical height loss was not reliable. Increasing age correlated only weakly with clinical osteoporosis.Conclusion: These are modest numbers from a nonacademic referral practice and may not be typical of other populations. Thirty-six percent of our patients were misclassified by DXA alone, with fragility fractures already taken into account for T-scores of -1.5 and lower. FRAX, height loss, age, back pain, and fragility fractures all failed to identify many of the patients identified by VFA. Seeing the lateral spine images obtained by VFA influenced patients and families. VFA on all first-time patients should be reconsidered.Abbreviations:BMD = bone mineral density; DXA = dual-energy X-ray absorptiometry; FRAX = Fracture Risk Assessment Tool; HL = height loss; ISCD = International Society for Clinical Densitometry; VF = vertebral fracture; VFA = vertebral fracture assessment     

Bone Mineral Density in Patients with Nonalcoholic Steatohepatitis among End-Stage Liver Disease Patients Awaiting Liver Transplantation

ObjectiveSeveral studies have shown that patients with end-stage liver disease (ESLD) have lower bone mineral density (BMD) and a higher prevalence of osteoporosis compared to an age-matched population. Hyperinsulinemia and insulin resistance are typically associated with increased BMD. We hypothesized that patients with nonalcoholic steatohepatitis (NASH) and underlying insulin resistance may have higher BMD than patients with cirrhosis from other causes.MethodsWe performed a retrospective chart review of patients with ESLD who underwent liver transplant evaluation at Ochsner Clinic Foundation and had a BMD study as part of initial work up and compared BMD values of patients diagnosed with NASH to patients with cirrhosis due to other causes. Patients were categorized into 3 groups based on the etiology of their liver disease as NASH, alcoholic cirrhosis, or viral hepatitis C or B (HCV/ HBV).ResultsA total of 63 patients met the study inclusion criteria, including 15 with NASH, 17 with alcoholic cirrhosis, and 31 with HCV/HBV. The overall prevalence rates of osteopenia and osteoporosis were 44% and 12%, respectively. BMD values were higher in the NASH group than the HCV/HBV group at lumbar spine, total hip, and femoral neck (P = .01, .03, and .02, respectively). There were no statistical differences in BMD values between NASH and alcoholic cirrhosis groups at any site.ConclusionsWe found a high prevalence of low BMD among patients with ESLD awaiting liver transplantation. NASH patients had higher BMDs than HCV/ HBV patients. The effects of NASH and insulin resistance on bone are complex and should be examined further. (Endocr Pract. 2013;19:414-419)     

Can self-rated health identify us women and men with low bone mineral density? a cross-sectional population study

Background: Despite its simplicity, self-rated health (SRH) is a significant dimension of health assessment, with demonstrated means to identify individuals at increased risk of morbidity and mortality.Objective: The aim of the present study was to assess whether SRH, age, and modifiable osteoporosis risk factors in a hypothetical screening situation could identify individuals with low bone mineral density (BMD).Methods: Data were analyzed from a multiethnic sample of 4905 women and men aged 50 to 79 years from the Third National Health and Nutrition Examination Survey. Low BMD was assessed according to the World Health Organization definition using gender- and race/ethnicity-specific young adult mean values to calculate T-scores. Multiple linear regression analysis was used to determine whether BMD was lower among those with poorer SRH; multiple logistic regression analysis was used to determine whether poor SRH was associated with low BMD.Results: The study population included 616 and 589 African American; 522 and 564 Mexican American; and 1312 and 1302 white women and men, respectively. The distributions of SRH responses differed for African American and Mexican American women and men compared with the distributions for samegender whites, with significantly more white women and men reporting excellent or very good health (P < 0.05) and significantly greater proportions of African American and Mexican American women and men reporting poorer health (P < 0.05). Among women and nonwhite men, there was no evidence of an association between BMD and SRH. Linear trends of decreasing BMD with declining SRH were detected for all men with low or normal body mass index (P < 0.001) and overweight men (P < 0.001). When stratified by race/ethnicity, a linear trend of decreasing BMD with declining SRH was found for nonobese white men only (P-trend: <0.001). The likelihood of having low BMD among nonobese white men who reported excellent or very good health was two-thirds that of their male counterparts with poor SRH (P < 0.001).Conclusions: Independent of age and modifiable osteoporosis risk factors, poor SRH may be a relevant risk factor for low BMD among older nonobese white men. Further research is needed to determine whether SRH may be a useful risk assessment tool for low BMD in this group of men.     

Trabecular Bone Score in Patients with Normocalcemic Hyperparathyroidism

Objective: The effects of normocalcemic hyperparathyroidism (NHPT) on bone remain unclear. The objective of this study was to evaluate differences in the trabecular bone score (TBS) of NHPT patients and asymptomatic hypercalcemic hyperparathyroidism (HHPT) patients.Methods: We performed a prospective study that enrolled consecutive patients with asymptomatic hyperparathyroidism (NHPT and HHPT) with a follow-up ≥1 year at the University Hospital of Valladolid, Spain. Metabolic phosphocalcium plasma and urine parameters were evaluated in ≥2 determinations during follow-up to classify patients as NHPT patients or asymptomatic HHPT patients. A control group was enrolled during the same period. TBS and bone mineral density (BMD) were evaluated.Results: Thirty-nine patients with asymptomatic HPT (24 with NHPT and 15 with HHPT) and 24 controls were recruited. NHPT patients and HHPT patients had a similar mean age, vitamin D level, TBS, and areal BMD (all sites). Compared to controls, symptomatic HPT patients had significantly higher parathyroid hormone (PTH) and calcium levels and significantly lower TBS and areal BMD at all sites (all P<.05). A significant negative relationship between TBS and PTH was found in asymptomatic HPT patients (r = -0.320, P = .043), which remained significant after adjustment for age, sex, and body mass index.Conclusion: There was no difference in the TBS between NHPT and HHPT patients. However, there was a reduction in the TBS of patients with asymptomatic HPT that was related to PTH levels but had no repercussion on bone mass. Higher levels of PTH seem to be responsible for this alteration in microarchitecture texture.Abbreviations:aBMD = areal bone mineral densityBMD = bone mineral densityBMI = body mass indexDXA = dual-energy X-ray absorptiometryHHPT = hypercalcemic hyperparathyroidismHPT = hyperparathyroidismHR-MRI = high-resolution magnetic resonanceHR-pQcT = high-resolution peripheral quantitative computed tomographyNHPT = normocalcemic hyper-parathyroidismPTH = parathyroid hormoneTBS = trabecular bone score25vitD = 25-hydroxyvitamin D