Virtual Orthopedic-Rehabilitation-Metabolic Collaboration for Treating Osteoporotic HIP Fractures

Objective: To evaluate the effectiveness of a virtual, closed-loop protocol that treated hip fracture patients without formal clinic visits.Methods: In this prospective cohort study, an intervention group of 85 hip fracture patients (33.6%) with vitamin D levels ≥65 nmol/L who received recommendations for osteoporosis treatment, was compared to a nonintervention group of 168 (66.4%), with vitamin D <65 nmol/L. Treatment included vitamin D loading in orthopedic and rehabilitation departments for patients from both groups, and virtual, osteoporosis treatment recommendations by Metabolic Clinic physicians to patients from the intervention group upon achieving a vitamin D level ≥65 nmol/L. Recommendations were given without requiring clinic visits. Osteoporosis drug recommendations were relayed to primary care physicians. The primary endpoint was patients receiving osteoporosis drugs within 12-months post-surgery. Secondary endpoints were patients issued drugs within 3- and 6-months post-surgery, and 1-year post-fracture mortality rates.Results: Among 253 hip fracture patients (81.3 ± 10.7 years-of-age, 68.8% women), the postintervention osteoporosis medication issue rate was higher than in the nonintervention group (48.2% versus 22.0%, respectively; P<.001). More intervention group patients received drugs 3 months (18.8% versus 2.9%; P<.001) and 6 months after surgery (40% versus 5.9%; P<.001). One-year mortality was lower among patients who received any osteoporosis medications (either through our intervention or from community physicians) than among untreated patients (5.1% versus 26.3%; P<.001).Conclusion: Virtual orthopedic-rehabilitation-metabolic collaboration increased osteoporosis treatment rates post-hip fracture. Yet, treatment rates remained <50%. Additional research is required to increase treatment rates further, such as providing drug therapy shortly after surgery, perhaps during rehabilitation, or lowering the vita-min D threshold.Abbreviations: CHS = Clalit Health Services; FLS = Fracture liaison service; HMO = Health Maintenance Organization; MMC = Meir Medical Center; PCP = primary care physician     

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     

The Associations Between Hypovitaminosis D,Higher Pth Levels With Bone Mineral Densities,And Risk Of The 10-Year Probability Of Major Osteoporotic Fractures In Chinese Patients With T2Dm

Objective: In the current study, we investigated the vitamin D status, and its relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD), and the 10-year probability of fractures in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: This was a cross-sectional study of 785 patients. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D (25(OH)D) and intact PTH were also quantified. The 10-year probability of fracture risk (major osteoporotic fracture &lsqb;MOF] and hip fracture &lsqb;HF]) was assessed using the fracture risk assessment tool (FRAX).Results: The prevalence of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 ± 15.2 nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk than the inadequate groups. Lower 25(OH)D was associated with higher PTH (r = -0.126, P<.001). PTH was negatively correlated with BMDs at 3 sites and positively correlated with MOF and HF, but this relationship disappeared in the adequate subgroup. Multivariate stepwise regression analysis revealed that PTH was the determinant of MOF (standard β = 0.073, P = .010) and HF (standard β = 0.094, P = .004).Conclusion: Our results identified a significantly high rate of vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk factor responsible for the higher 10-year probability of osteoporotic fractures in diabetic patients, especially in those with lower vitamin D levels.Abbreviations: AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine; MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus; PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA = uric acid     

A Simple Intervention for Improving the Implementation Rate of a Recommended Osteoporosis Treatment After Hip Fracture

ObjectiveOsteoporosis is often under-treated, and hip fracture is frequently its first manifestation. Hospitalization for a hip fracture is an opportunity to initiate osteoporosis treatment. The aim of this study was to investigate whether a simple intervention improves the implementation rate of a recommended osteoporosis treatment.MethodsOne hundred elderly patients admitted with low-impact hip fracture were given a 10 minute explanation about osteoporosis and its treatment during their postoperative hospital stay. In addition, the patients received an explanatory brochure and a letter to their primary care physician that included an article on fracture rate reduction with osteoporosis treatment. Implementation of therapy was assessed by a telephone survey 3 and 6 months postoperatively. The patients who had not received treatment at 3 months were given a repeated explanation. The historical control group was comprised of 100 hip fracture patients with similar demographic characteristics, who were operated on and discharged with the standard care recommendations for osteoporosis prevention.ResultsAt the 3 month follow-up, the therapy rate in both groups was similar (19%). Fifty-eight percent of the patients in the study group had no recollection of the intervention. However, after a repeated explanation, at the 6 month follow-up, 39% of the intervention group had received drug therapy for fracture prevention (P<.001).ConclusionA simple intervention enlisting the patients' help to involve their primary care physician can increase treatment rates for osteoporosis following a hip fracture. During the immediate postoperative period, the patients and their families have difficulty implementing the recommendations. Therefore, repeated communications are recommended. (Endocr Pract. 2013;19:46-50)     

Osteoporosis Treatment After Osteoporotic Fractures: Data From a Single Medical Center

ObjectiveMost patients do not receive osteoporosis treatment after osteoporotic fracture. This study reviewed osteoporosis treatment after osteoporotic fractures in a center without a Fracture Liaison Service.MethodsWe identified all patients with hip, vertebral, humeral or radial fractures, evaluated in Meir Medical Center, in 2017. The exclusion criteria were not a Clalit Health Services member, high-energy fracture or 30-day postoperative mortality. The primary endpoint was osteoporosis drugs issued within 12 months of fracture. Secondary endpoints included bone densitometry and 1-year mortality.ResultsFive-hundred-eighty-two patients (average age 78.6 ± 11.1 years, 75.8% women) were included. There were 321 (55.5%) hip, 84 (14.1%) humeral, 33 (5.6%) vertebral, and 144 (24.7%) radial fractures. Osteoporosis drugs were issued to 26.5% of the patients; those with humeral fractures received the least (21.4%) and vertebral, the most (30.3%; P = .51). Bone densitometry was performed in 23.2% of patients. One-year mortality after hip fracture was 12.1%, followed by humeral (3.6%; P < .05). Logistic regression showed that previous treatment (odds ratio [OR] = 7.4; 95% confidence interval [CI] 3.6–15.2), bone densitometry (OR = 4.4; 95% CI 2.6–7.4) and endocrinology visit (OR = 2.6; 95% CI, 1.4–4.6) were the most important factors associated with treatment.ConclusionFewer than one third of patients received pharmacotherapy within 1 year after fracture. Because pharmacotherapy reduces future fractures and mortality, we recommend that medical staff who care for patients with fracture adopt practical and effective strategies to increase treatment rates among patients with osteoporotic fractures.     

Effect of Vitamin D Therapy on Bone Turnover Markers in Postmenopausal Women with Osteoporosis and Osteopenia

ObjectiveTo (7) assess the rate of reduction in bone turnover with vitamin D and bisphosphonate therapies and (2) evaluate the clinical utility of bone-specific alkaline phosphatase (BSAP) in monitoring treatment response.MethodsWe retrospectively reviewed medical records of patients with newly diagnosed osteopenia and osteoporosis from 2002 to 2009 at Loyola University Medical Center. A cohort of postmenopausal women with hip or spine T-scores of less than -1, normal serum creatinine, and no prior vitamin D or bisphosphonate therapy was divided into vitamin D-deficient (n = 29) and vitamin D-sufficient (n = 13) groups. Vitamin D-deficient patients received high-dose vitamin D, whereas vitamin D-sufficient patients received orally administered bisphosphonates. BSAP levels at baseline and 1 year were compared.Resultsvitamin D therapy in the group with vitamin D deficiency led to a 26.7% decrease in BSAP (P < .01). Bisphosphonate therapy in the vitamin D-sufficient group led to a 32.7% decrease in BSAP (P = .01). The magnitude of BSAP change in the 2 study groups (6.74 ± 6.48 μg ∕ L and 8.72 ± 9.94 μgZL) did not differ significantly (P = .45).ConclusionThe results of this study suggest that correction of vitamin D deficiency in patients with osteopenia and osteoporosis can lead to a decrease in bone turnover as measured by BSAP and that the magnitude of this reduction is similar to that achieved with orally administered bisphosphonates. (Endocr Pract. 2011;17:873-879)     

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     

Assessment of Inpatient Fragility Fracture Education and Outpatient Follow-Up at an Urban Tertiary Care Institution

ObjectiveTo assess the impact of inpatient fragility fracture education on follow-up care at an urban tertiary care center with a multidisciplinary inpatient education and follow-up initiative.MethodsParticipants included 139 patients with lowenergy fragility fractures who were identified, educated, and referred for follow-up by a coordinator. Education consisted of an initial 30 to 40-minute session with the patient and family followed by 10-minute sessions on subsequent hospitalization days. Follow-up activities with primary care physicians (PCPs) and orthopaedic surgeons were documented.ResultsOf the 129 patients still living at the end of the study period, 74 (57%) had followed up with their PCP while 93 (72%) had returned to see their orthopaedic surgeons. Women were 2.7 times more likely than men to address the cause of the fragility fracture (95% confidence interval [CI], 1.13-6.97; P = .038) and were 6.18 times more likely to receive treatment or to have bone mineral density (BMD) testing (95% CI, 1.29-29.61; P = .023). Patients previously treated for osteoporosis were 3 times more likely to follow-up with their PCPs (95% CI, 1.10- 8.02; P = .02), while patients who had previous BMD tests were 4.9 times more likely to follow-up (95% CI, 1.89- 12.79; P = .001). We observed a 42% reduction in the likelihood of seeing a physician for osteoporosis evaluation for each additional 10 years of age (95% CI, 13%-61% reduction in odds; P = .008).ConclusionIn the urban setting, follow-up rates are not sufficiently improved by inpatient education. Improved, persistent communication between the orthopaedic surgeon, PCP, and patient is needed to effectively treat patients and prevent future fractures. (Endocr Pract. 2008;14:58-68)     

Hypoglycemia Rates After Restriction of High-Dose Glargine in Hospitalized Patients

Objective: Hypoglycemia remains one of the main challenges of insulin therapy. To reduce insulin-related hypoglycemia at our institution, we restricted inpatient ordering of high glargine doses (≥0.5 U/kg/day) to endocrine staff in May 2013. This retrospective cohort study assesses its effect on hypoglycemia and glycemic control within 48 hours of admission (ADM).Methods: We identified 692 adult patients hospitalized at Boston Medical Center who received glargine upon ADM from November 1, 2012 through April 30, 2013 as the pre-intervention group, and 651 adult patients admitted between November 1, 2013 and April 30, 2014 as the postintervention group. Demographics, medical history, home insulin regimen, concurrent oral diabetes medications or glucocorticoid administration, ADM serum creatinine, all blood glucose levels (BG) ≤48 hours of ADM, and hemoglobin A1c values ≤3 months were assessed. Hypoglycemia was defined as BG ≤70 mg/dL, and hyperglycemia as BG ≥200 mg/dL. Multivariable regression models assessed potential associations between covariates and incidence of hypoglycemia and average BG ≤48 hours of ADM.Results: Demographics were similar between groups. Significantly less patients received high-dose glargine in the post-intervention group (5.2% vs. 0.3%, P<.001). Incidences of hypoglycemia were significantly lower in the postintervention group (20.9% vs. 17.8%, P<.001 per ADM; 3.4% vs. 2.3%, P = .001 per BG measurements [BGM]). Mean BG levels ≤48 hours of ADM and incidence of hyperglycemia were not significantly different. The adjusted incident rate ratio of hypoglycemia was 0.63 per ADM and 0.74 per BGM in the postintervention group compared to the pre-intervention group (P = .001 and P = .063, respectively).Conclusion: We found that implementation of a restriction on high doses of glargine resulted in lower rates of hypoglycemia without worsening glycemic control.Abbreviations:ADM = admissionBG = blood glucoseBGM = blood glucose measurementsBMC = Boston Medical CenterBMI = body mass indexEMR = electronic medical recordHgbA1c = hemoglobin A1cIRR = incidence rate ratioNPH = neutral protamine HagedornTDD = total daily doseT2D = type 2 diabetes     

Osteoporosis in Men

ObjectiveTo review information pertinent to bone health and osteoporosis in men.MethodsA review of pertinent literature was conducted.ResultsOsteoporosis affects approximately 2 million men in the US and accounts for an estimated 600,000 fractures each year. There are significant differences in skeletal size and structure between men and women that account for differences in fracture incidence, location, and outcomes. Bone density testing is appropriate for men age 70 and older and younger men (50-69) who have risk factors for osteoporosis. Lifestyle management, including adequate calcium and vitamin D intake, appropriate physical activity, and avoidance of tobacco and heavy alcohol use, is appropriate for all men. Pharmacologic therapy to reduce fracture risk is advisable for men with a clinical diagnosis of osteoporosis (a spine or hip fracture) or a T-score of −2.5 or below in the spine, femoral neck, total hip or 1/3 radius; however, the majority of men at high risk will only be identified using a fracture risk assessment tool, such as FRAX. Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options.ConclusionOsteoporosis in men presents an important public health problem with significant morbidity and mortality. There are recommended strategies for identifying men at high risk of fracture, and effective agents are available for treatment. (Endocr Pract. 2013;19:834-838)     

Effectiveness and Outcomes of Current Practice in Treating Vitamin D Deficiency in Patients Listed for Liver Transplantation

Objective: Vitamin D deficiency is prevalent in cirrhotic patients awaiting liver transplantation (LT). Optimal vitamin D management for these patients remains undefined. We sought to determine the effectiveness of our practice in addressing vitamin D deficiency in LT patients.Methods: This retrospective study included 127 patients who received a first LT between July 2010 and July 2011. Outcomes measured included readmission rates, fractures, and functional status post-LT. 25-Hydroxyvitamin D (25-OH D) deficiency was stratified as: mild (20–30 ng/mL), moderate (15–19.9 ng/mL), and severe (<15 ng/mL). We estimated the amount of vitamin D supplementation required for each patient.Results: At LT evaluation, 107 patients (84%) had vitamin D deficiency, and 74% remained vitamin D deficient at LT. Only 62% received vitamin D supplementation pre-LT. Moderate and severe deficiencies were less common at LT and rare 4 months post-LT. There was an association between improvement in vitamin D deficiency category at LT and increased vitamin D (>400,000 IU total) supplementation (P = .004). We found no association between vitamin D deficiency at LT and functional status, fractures, or readmissions post-LT. Patients receiving induction immunosuppressant therapy with basiliximab had a significantly greater degree of worsening in bone mineral density (BMD) post-LT.Conclusion: Moderate-to-severe vitamin D deficiency was very prevalent in a cohort of patients undergoing evaluation for LT. Deficiency was improved with increased vitamin D replacement therapy. Vitamin D deficiency at LT was not associated with worse bone or functional outcomes post-LT. The influence of basiliximab on bone health post-LT requires further evaluation.Abbreviations: 25-OH D = 25-hydroxyvitamin D BMD = bone mineral density BMI = body mass index CI = confidence interval LT = liver transplantation MELD = Model for End-Stage Liver Disease PTH = parathyroid hormone     

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     

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 of Body Mass Index and Age with Osteoporosis Probability in Patients with Primary Hyperparathyroidism

ObjectiveCurrently, there are limited markers to predict the osteoporosis probability in patients with primary hyperparathyroidism. We studied the relationship between various parameters and results of DXAs at various skeletal sites.MethodsRetrospective review of data for 218 patients with primary hyperparathyroidism was performed. Age, BMI, bone mineral density, serum total calcium, ionized calcium, intact parathyroid hormone, albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-hour urinary calcium levels and parathyroid tumor weight were analyzed. Two different statistical models- linear regression and multivariate logistic regression were performed.ResultsAt the lumbar spine, with the linear model, BMI (P < .001), alkaline phosphatase (P < .001), and ionized calcium (P < .001) significantly correlated with T scores; whereas with the logistic model, BMI was the only variable predicting osteoporosis probability.At the femoral neck, BMI (P < .022), 25-hydroxy vitamin D (P < .001), 1,25-dihydroxy vitamin D (P < .034) correlated with T scores; whereas both BMI (P < .029) and age (P < .051) were the significant variables that predicted osteoporosis.At the total hip, BMI (P < .001) and age (P < .001) correlated with T scores; whereas with the logistic model, only BMI (P < .016) predicted osteoporosis. At the forearm, a model could not be generated due to limited number.ConclusionIn patients with primary hyperparathyroidism, BMI strongly correlated with T scores and probability of osteoporosis.     

A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology,Rheumatoid Arthritis cohort study

Introduction

Vitamin D deficiency has been reported to be common in patients with rheumatoid arthritis (RA) who have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Genetic variants affecting serum 25-hydroxyvitamin D (25(OH)D) concentration, an indicator of vitamin D status, were recently identified by genome-wide association studies of Caucasian populations. The purpose of this study was to validate the association and to test whether the serum 25(OH)D-linked genetic variants were associated with the occurrence of hip fracture in Japanese RA patients.

Methods

DNA samples of 1,957 Japanese RA patients were obtained from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort DNA collection. First, five single nucleotide polymorphisms (SNPs) that were reported to be associated with serum 25(OH)D concentration by genome-wide association studies were genotyped. The SNPs that showed a significant association with serum 25(OH)D level in the cross-sectional study were used in the longitudinal analysis of hip fracture risk. The genetic risk for hip fracture was determined by a multivariate Cox proportional hazards model in 1,957 patients with a maximum follow-up of 10 years (median, 8 years).

Results

Multivariate linear regression analyses showed that rs2282679 in GC (the gene encoding group-specific component (vitamin D binding protein)) locus was significantly associated with lower serum 25(OH)D concentration (P = 8.1 × 10^-5). A Cox proportional hazards model indicated that rs2282679 in GC was significantly associated with the occurrence of hip fracture in a recessive model (hazard ratio (95% confidence interval) = 2.52 (1.05-6.05), P = 0.039).

Conclusions

A two-staged analysis demonstrated that rs2282679 in GC was associated with serum 25(OH)D concentration and could be a risk factor for hip fracture in Japanese RA patients.     

Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBDs): What the Endocrinologist Needs to Know

ObjectiveChronic kidney disease-mineral and bone disorders (CKD-MBDs) are a spectrum of abnormalities involving skeletal hormones, minerals, and bone turnover and mineralization. This paper focuses on what the endocrinologist should know about the assessment and management of skeletal and metabolic disorders in CKD-MBDs.MethodsRelevant literature was reviewed to (1) define disturbances of minerals and hormones in the course of CKD; (2) identify the variable radiographic and histomorphometric changes of CKD-MBDs; (3) review the association among CKD-MBDs, vascular calcification, cardiovascular disease (CVD), and mortality; and (4) clarify issues in CKD-MBDs therapy.ResultsAssessment and treatment of CKD-MBDs is complicated by progressive changes in bone minerals and skeletal regulatory hormones as kidney function declines. CKD-MBDs are associated with fracture risk, and studies demonstrate that bone mineral density can be used to assess bone loss and fracture risk in these patients. Treatment of CKD-MBDs continues to evolve. Use of calcium, phosphate binders, vitamin D, vitamin D–receptor analogs, and drugs for osteoporosis and CKD-MBDs treatment are discussed in the context of safety and efficacy for patients with CKD.ConclusionThe association of CKD with bone disease, vascular calcification, CVD, and mortality mandates earlier recognition and treatment of CKD-MBDs. Osteoporosis as a distinct entity can be diagnosed and managed in CKD, although assessment of osteoporosis becomes challenging in late (stage 4 to 5) CKD. Diabetes is common in early (stage 1 to 3) CKD. In addition, 96% of all individuals identified as having CKD have early CKD. The endocrinologist is uniquely positioned to address and treat both diabetes and many of the metabolic and skeletal disorders associated with early CKD-MBDs, including osteoporosis. (Endocr Pract. 2014;20:500-516)     

Increase in Bone Mass After Correction of Vitamin D Insufficiency in Bisphosphonate-Treated Patients

ObjectiveTo assess the relative contribution of vitamin D insufficiency to loss of bone mineral density (BMD) in patients taking bisphosphonates.MethodsPatients were eligible for inclusion if they had osteoporosis or osteopenia and demonstrated a decline in BMD during the preceding year while taking stable doses of alendronate or risedronate, plus supplemental calcium and vitamin D. Patients with previously known secondary causes of osteoporosis were excluded from the study. Eligible patients underwent prospective measurement of bilateral hip and lumbar spine BMD by dual-energy x-ray absorptiometry, serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D, intact parathyroid hormone, osteocalcin, and thyroid-stimulating hormone (thyrotropin), and urinary calcium:creatinine ratio.ResultsAnnual BMD was assessed in 175 previously bisphosphonate-responsive patients with low BMD. Of the 175 patients, 136 (78%) had either a significant interval increase or no change in BMD, whereas 39 (22%) had a significant decrease. Of the 39 patients who lost BMD, 20 (51%) had vitamin D insufficiency (25-OHD < 30 ng/mL). After a single course of orally administered vitamin D₂ (500,000 IU during a 5-week period), the 25-OHD level returned to normal in 17 of the 20 vitamin D-insufficient patients and was associated with significant (P < .02) 3.0% and 2.7% increases in BMD at the lumbar spine and the femoral neck, respectively. Failure to normalize the serum 25-OHD level was associated with further loss of BMD.ConclusionVitamin D insufficiency was the most frequently identified cause of bone loss in patients with declining BMD during bisphosphonate therapy. Correction of vitamin D insufficiency in these patients led to a significant rebound in BMD. (Endocr Pract. 2008; 14:293-297)     

In Situ Detection of 1,25-dihydroxyvitamin D Receptor In human Skeletal Muscle Tissue

Growing evidence suggests that intracellular vitamin D receptors are present in skeletal muscle tissue mediating vitamin D hormone response. The aim of the work reported here was to investigate the in situ expression of 1,25-dihydroxy vitamin D₃ receptor in human skeletal muscle tissue. Intraoperative periarticular muscle biopsies were taken from 20 female orthopaedic patients (17 middle-aged and elderly patients receiving total hip arthroplasty due to osteoarthritis of the hip or an osteoporotic hip fracture and 3 young patients who received back surgery). The immunohistological distribution of the vitamin D₃ receptor was investigated using a monoclonal rat antibody to the receptor (Clone Nr. 9A7). The receptor-positive nuclei were quantified by counting 500 nuclei per biopsy. Strong intranuclear immunostaining of the vitamin D receptor was detected in human muscle cells. Biopsies of hip patients had significantly fewer receptor-positive nuclei compared to those of back surgery patients (Mann–Whitney U-test: p = 0.0025). VDR expression (number of antigen-positive nuclei) was significantly correlated with age (coefficient of correlation = 0.46; p = 0.005), but not with 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels. The data clearly demonstrate presence of nuclear 1,25-dihydroxyvitamin D₃ receptor in human skeletal muscle. To our knowledge this is the first in situ detection of the receptor in human skeletal muscle. The difference in the expression of the receptor between hip and spinal muscle biopsies might be explained by age or location. Further research is needed in order to evaluate whether vitamin D₃ receptor expression in human skeletal muscle is age-dependent and varies between different muscles.     

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     

Vitamin d status and its relationship with bone mineral density and parathyroid hormone in southeast asian adults with low bone density

ObjectiveTo investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore.MethodsIn total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD.ResultsThe mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine(P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip(P = .035) and the lumbar spine (P = .019). At levels < 30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036).ConclusionAmong this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations < 30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health. (Endocr Pract. 2011;17:226-234)