Abnormalities of Vitamin D and Calcium Metabolism after Surgical Treatment of Morbid Obesity: A Study of 136 Patients

ObjectiveTo assess the effect of bariatric surgical treatment of morbid obesity on bone mineral metabolism.MethodsWe analyzed pertinent vitamin D and calcium metabolic variables in 136 patients who had undergone a malabsorptive bariatric operation. Measurements of bone mineral density (BMD), serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D [1,25-(OH)₂D], parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase were performed. Statistical analyses assessed correlations among various factors.ResultsThe mean age (± SD) of the study group was 48.34 ± 10.28 years. Their mean weight loss was 114.55 ± 45.66 lb, and the mean duration since the bariatric surgical procedure was 54.02 ± 51.88 months. Seventeen patients (12.5%) had a T-score of -2.5 or less, and 54 patients (39.7%) had a T-score between –1.0 and –2.5. Of 119 patients in whom serum 25-OHD was measured, 40 (34%) had severe hypovitaminosis D (25-OHD < 8 ng/mL), and 50 patients (42%) had low hypovitaminosis D (serum 25-OHD 8 to 20 ng/mL). The magnitude of weight loss correlated negatively with serum 25-OHD, calcium, phosphorus, and calcium × phosphorus product values and positively with serum alkaline phosphatase level. Serum 25-OHD and calcium concentrations correlated positively with the BMD. PTH, serum 1,25-(OH)₂D, and alkaline phosphatase concentrations correlated negatively with the BMD, a reflection of the presence of secondary hyperparathyroidism, an accelerated conversion of 25-OHD to 1,25-(OH)₂D by the elevated PTH levels, and increased osteoblastic activity. The mean daily vitamin D supplementation was 6,472 ± 9,736 IU.ConclusionHypovitaminosis D and subsequent bone loss are common in patients who have undergone a bariatric surgical procedure for morbid obesity. These patients require rigorous vitamin D supplementation. (Endocr Pract. 2007;13:131-136)     

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm²).ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)     

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     

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.     

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)     

经皮椎体成形术治疗骨质疏松性椎体压缩骨折的临床疗效及术后邻近椎体骨折的危险因素分析

摘要 目的：观察骨质疏松性椎体压缩骨折（OVCFs）患者以经皮椎体成形术（PVP）治疗后的临床疗效,并分析术后邻近椎体骨折的危险因素。方法：选取我院2018年6月~2020年9月期间收治的OVCFs患者180例,给予PVP治疗,观察其治疗效果、骨水泥渗漏情况、术后邻近椎体骨折发生情况,采用单因素及多因素Logistic回归分析术后邻近椎体骨折的危险因素。结果：OVCFs患者术前~术后6个月功能障碍指数（ODI）、疼痛视觉模拟评分（VAS）、活动能力评分（LAS）均呈降低趋势（P＜0.05）。随访期间,180例患者中,15例（8.33%）出现了骨水泥渗漏,但均不需要进一步处理。32例（17.78%）出现了术后邻近椎体骨折,148例未出现术后邻近椎体骨折,并以此进行分组。再骨折组、未再骨折组在年龄、骨折病史、骨密度、Cobb角、椎体高度恢复、骨水泥渗漏情况、使用抗骨质疏松药物方面对比有明显差异（P<0.05）。年龄>70岁、骨水泥渗漏、骨密度<-2.5SD、未使用抗骨质疏松药物、Cobb角<15°、椎体高度恢复率>87%均是PVP术后邻近椎体骨折的危险因素（P<0.05）。结论：PVP治疗OVCFs疗效较好,可缓解患者疼痛、减轻功能障碍、改善活动能力,术后邻近椎体骨折的发生受年龄、骨密度、Cobb角等多种因素影响,临床可针对这些因素给予对应的干预措施。     

Teriparatide as a Systemic Treatment for Lower Extremity Nonunion Fractures: A Case Series

ObjectiveTo investigate the effect of teriparatide (parathyroid hormone [1-34]) on the healing of long bone nonunion fractures.MethodsWe performed a retrospective chart review of patients with fracture nonunion, aged 10 to 99 years who were treated with teriparatide at the Children’s Hospital of Philadelphia or the Hospital of the University of Pennsylvania between November 2002 and January 2013. The primary endpoints were radiographic evidence of callus formation and fracture union, ability to bear weight without affected limb limp, and normal range of motion and strength.ResultsSix patients aged 19 to 64 years with tibial or femoral fractures that had not healed for 3 to 36 months were treated with teriparatide 20 μg/day. Accelerated healing of fracture nonunion was confirmed in 5 of 6 patients with time to complete union of 3 to 9 months. The shortest time to recovery was observed in younger patients without comorbidities. Treatment was well tolerated.ConclusionTeriparatide is a promising treatment for nonunion fractures, but its response depends on associated comorbidities. The potential benefit of teriparatide as an adjunct to treat nonunion justifies randomized placebo-controlled trials to determine its efficacy and safety in broader populations. (Endocr Pract. 2015;21:136-142)     

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     

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     

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)     

Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?

Objective:We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week’s post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT).Methods:Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6^th and 12^th week on the fractured side.Results:39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss.Conclusion:Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.     

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     

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     

The 25-hydroxyvitamin D threshold for better health

Available data supporting a target serum level of at least 75 nmol/l 25-hydroxyvitamin D (25-OHD) include studies on bone mineral density (bmd), fracture prevention, lower extremity function, and cancer prevention. Given the high cost and disability from falls, fractures, and cancer treatment a shared threshold for 25-OHD has significant public health implications, especially so, if a large part of the population is below this threshold. This article summarizes available evidence supporting the 75 nmol/l threshold, reviews adherence to Vitamin D treatment in fracture trials in regard to achieved anti-fracture efficacy, and finally discusses current recommendations for Vitamin D intake.     

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)     

Vitamin D Deficiency in Children with a Chronic Illness–Seasonal and Age-Related Variations in Serum 25-hydroxy Vitamin D Concentrations

Introduction

Children and adolescents with a chronic illness have potential risk factors for vitamin D deficiency. An optimal vitamin D status might have multiple health effects. This study evaluated vitamin D status and its association with age, gender, and season in a large cohort of chronically ill Finnish patients at a tertiary pediatric outpatient clinic. A cross-sectional register-based study was carried out, involving altogether 1351 children (51% boys, age range 0.2–18 years), who visited the outpatient clinic during 2007–2010 and had their vitamin D status (S-25-OHD) determined. A post-doc analysis was conducted to identify predisposing and preventing factors for vitamin D deficiency.

Results

Almost half (47%) of the S-25-OHD values were consistent with subnormal vitamin D status (S-25-OHD <50 nmol/L) while only 12% were >80 nmol/L. Age and season were the most important determinants for S-25-OHD concentration. Mean S-25-OHD concentration differed between age groups (Kruskal-Wallis; p<0.001), adolescents being at highest risk for vitamin D insufficiency. Young age and vitamin D supplementation were preventive factors for deficiency, while non-Finnish ethnic background was a predisposing factor. S-25-OHD showed significant seasonal variation in children older than 6 years. In the whole cohort, S-25-OHD was on average 13 nmol/L higher in summer than in winter, and the prevalence of vitamin D deficiency ( =  S-25-OHD <37.5 nmol/l) varied from 11% in summer to 29% in winter.

Conclusions

The finding that almost half of the studied Finnish children with a chronic illness had suboptimal vitamin D status is alarming. Inferior vitamin D status was noted in adolescents compared with younger children, suggesting that imbalance between intake and requirement evolves with age. Although less common during summer, subnormal vitamin D status was still observed in 28% of those evaluated in summer. Clinicians should identify individuals at risk and actively recommend vitamin D supplementation.     

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     

The Risk Factors for Developing Clustered Vertebral Compression Fractures: A Single-Center Study

ObjectiveVertebral compression fractures (VCFs) are common among elderly individuals, but clustered VCFs (C-VCFs) are rare and more severe. The risk factors for C-VCFs remain unclear. Thus, we investigated the clinical characteristics of C-VCFs to identify the imminent fracture risk and improve the treatment for such patients.MethodsWe reviewed the records of patients with VCF at a single medical center between January 2011 and September 2020. Patients who had 4 or more VCFs within 1 year were categorized into the C-VCF group, and the remaining patients were paired into the control group at a ratio of 2:1. We collected demographic, clinical, laboratory, and radiologic information regarding these patients. Univariate analyses, stratified analyses, and multivariate logistic regression were performed to identify the risk factors for C-VCFs.ResultsA total of 156 patients were enrolled, of whom 52 were patients with C-VCF. Patients with C-VCF had more severe fractures and pain, with fractures occurring at uncommon sites of the spine. The independent risk factors for C-VCFs included glucocorticoid (GC) treatment (P < .001; hazard ratio [HR], 12.7), recent fracture history (P = .021; HR, 5.5), and lower trabecular bone score (TBS) (P = .044; HR, 1.6). TBS and bone mineral density had greater predictive values in patients without GC treatment (P < .001). Sex, age, and bone turnover biomarkers were not independent risk factors for C-VCFs.ConclusionC-VCFs are rare adverse consequences of severe osteoporosis, for which GC treatment, recent fracture history, and lower TBS are unique risk factors that are valuable for the early identification and prevention of C-VCFs.     

Adult Hypophosphatasia Treated with Teriparatide: Report of 2 Patients and Review of the Literature

Objective: Hypophosphatasia (HPP) is a rare inherited metabolic bone disease from deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Reportedly, teriparatide (parathyroid hormone 1–34) can benefit the adult form of HPP, including fracture healing. We studied 2 women with adult HPP given teripa-ratide and reviewed the reports of 6 additional patients.Methods: A 68-year-old black woman (patient 1) described low-trauma fractures and had subnormal serum alkaline phosphatase (ALP) activity. Biochemical findings were consistent with HPP. Mutation analysis revealed a heterozygous defect in exon 10 of TNSALP (ALPL). Teriparatide was injected daily for 2 years. Four years later, she fractured her right hip. Treatment was resumed for 8 months without further fractures. A 53-year-old white woman (patient 2) reported low-trauma fractures and had subnormal serum ALP. Mutation analysis revealed a heterozygous defect in exon 8 of TNSALP. She injected teriparatide daily for 2 years. One year later, bone mineral density (BMD) declined and treatment was resumed for 3 months. When she sustained a sacral fracture, teriparatide was administered for a further 18 months.Results: Patient 1's serum ALP increased while receiving teriparatide and returned to baseline after its discontinuation. BMD remained unchanged, but no fractures were sustained. Patient 2's serum ALP increased, but the improvement was not sustained. Femoral neck BMD increased significantly during the first cycle, declined significantly afterwards, and was regained during course of teriparatide.Conclusion: Teriparatide shows some benefit for adult HPP.Abbreviations:ALP = alkaline phosphataseBMD = bone mineral densityBSAP = bone-specific alkaline phosphataseCTX = C-telopeptideDXA = dual-energy X-ray absorptiometryFN = femoral neckHPP = hypophosphatasiaLS = lumbar spinePEA = phosphoethanolaminePLP = pyridoxal 5′-phosphatePTH = parathyroid hormoneSQ = subcutaneousTNSALP = tissue-nonspecific isoenzyme of alkaline phosphataseTPTD = teriparatide     

骨质疏松椎体压缩性骨折患者经皮椎体成形术后再次骨折的危险因素分析

目的:探讨骨质疏松椎体压缩骨折患者接受椎体成形术后再次新发骨折的危险因素。方法:选取2009年1月到2015年1月就诊于我院诊断为骨质疏松椎体压缩性骨折且行经皮椎体成形术的患者,收集患者的诊疗信息及影像学资料。收集患者的年龄、性别等基本资料及基于定量CT测量的骨矿物含量、骨水泥注射占椎体体积的比、骨水泥的分布及骨水泥的渗漏情况。将单椎体骨折且在随访时间内再次新发椎体骨折的患者分为A组,未骨折的患者分为B组,对比分析两组之间的参数的差异,并利用二项Logistic回归分析分析再次骨折的危险因素。结果:共有287例患者纳入研究,平均随访时间为34.7±17.8个月,压缩性骨折最常见的椎体依次为L1(29.1%)、T12(20.8%)及L2(13.5%)。在随访时间内共有32例患者再次发生椎体骨折。252例单椎体骨折患者中,26例(A组)再次发生骨折,226例(B组)未发生骨折。A组骨矿物含量低于B组(P0.001),骨水泥分布较B组差(P0.001),年龄高于B组(P0.001)且骨水泥渗漏发生率(34.6%)高于B组(13.7%)(P=0.006),两组在骨水泥占椎体的比、后凸程度、性别比例没有统计学差异。回归分析显示骨矿物含量(OR=1.092,P0.001)、年龄(OR=1.091,P0.001)及骨水泥渗漏(OR=1.200,P=0.002)均是再次骨折的危险因素,骨水泥的均匀分布是保护因素(OR=0.922,P0.001)。结论:年龄较大且骨质较差的患者容易再次发生椎体骨折,在行椎体成形术过程中应尽量使骨水泥均匀分布并避免骨水泥的渗漏。