Associations of different dietary patterns, bone mineral density, and fracture risk among elderly women: the China Osteoporosis Prevalence Study.

Objective: Despite the fact that China amounts to one-fifth of the world's population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men. Methods: Building upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant. Results: A diet rich in "carnivorous", "vegetarian", "dairy, fruit, and egg" was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1-4 (L1-4). Yet, a diet rich in "beverage and fried food" was associated with a lower BMD at the FN and L1-4. High quartiles of the carnivorous diet were associated with 34%-39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures. Conclusions: Our study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1-4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

Disruption of FLNB leads to skeletal malformation by interfering with skeletal segmentation through the HOX gene.

Filamin B (FLNB) plays an important role in skeletal development. Mutations in FLNB can lead to skeletal malformation such as an abnormal number of ossification centers, indicating that the skeletal segmentation in the embryonic period may be interfered with. We established a mouse model with the pathogenic point mutation FLNB NM_001081427.1: c.4756G > A (p.Gly1586Arg) using CRISPR-Cas9 technology. Micro-CT, HE staining and whole skeletal preparation were performed to examine the skeletal malformation. In situ hybridization of embryos was performed to examine the transcription of HOX genes during embryonic development. The expression of FLNB was downregulated in FLNBG1586R/G1586R and FLNBWT/G1586R mice, compared to FLNBWT/WT mice. Fusions in tarsal bones were found in FLNBG1586R/G1586R and FLNBWT/G1586R mice, indicating that the skeletal segmentation was interfered with. In the embryo of FLNBG1586R/G1586R mice (E12.5), the transcription levels of HOXD10 and HOXB2 were downregulated in the carpal region and cervical spine region, respectively. This study indicated that the loss-of-function mutation G1586R in FLNB may lead to abnormal skeletal segmentation, and the mechanism was possibly associated with the downregulation of HOX gene transcription during the embryonic period.

Effects of online continuing medical education on perspectives of shared decision-making among Chinese endocrinologists.

BACKGROUND: Shared decision-making (SDM) may influence the clinical outcomes of patients with endocrine disorders. There are few studies describing perspectives towards SDM among endocrinologists in China. METHODS: In the first stage, we conducted a national survey using an online questionnaire about SDM among endocrinologists in China. The national survey focused on attitude and propensity, potential barriers, and the effectiveness of SDM implementation strategies. In the second stage, survey participants were further recruited to participate in a prospective cohort study in the online continuing medical education (CME) program of Peking Union Medical College Hospital in Beijing. The Shared Decision-Making Questionnaire (SDM-Q-Doc) was employed to assess the effects of online CME on physicians' perspectives during the process of SDM, which was conducted before and after the CME course was provided. RESULTS: In the national survey, 280 endocrinologists (75.7% female, mean age 38.0 ± 4.5 years, 62.5% with a duration of practice of more than ten years) completed the questionnaire. Participants had a generally positive attitude towards SDM in clinical practice. The main perceived barriers included time consumption, information inequality between doctors and patients, and a lack of technical support and training for SDM. The main uncertainties of implementation steps included inviting patients to participate in SDM (16.3%), assisting in decision-making (15.3%), facilitating deliberation and decision-making (13.7%), and providing information on benefits and risks (12.6%). Of the physicians who participated in the national survey, 84 registered for the eight-day online CME course. The SDM-Q-Doc score increased from 87.3 ± 18.2 at baseline to 93.0 ± 9.3 at the end of the 8-day online CME training (p = 0.003, paired t test). The participants' age, sex, education level, practice duration, the annual number of patients with rare endocrine diseases, and the annual number of patients requiring MDT or CME were not significantly related to increased SDM-Q-Doc scores after online CME (all p > 0.05). CONCLUSIONS: Chinese endocrinologists had a generally positive attitude towards SDM in clinical practice. There were also several uncertainties in the implementation steps of SDM. Regardless of a physician's educational background or prior professional experience, CME may help to improve their perspectives regarding SDM.

Influence of Obesity and Changes in Weight or BMI on Incident Fractures in Postmenopausal Women: From Peking Vertebral Fracture Study.

This study aims to investigate the influence of overweight/obesity and change in weight or body mass index (BMI) on incident fractures among Chinese postmenopausal women. According to BMI, 754 postmenopausal women were categorized into normal weight (NW), overweight (OW), and obesity (OB) groups, respectively. We used data from the baseline and the second survey for statistical analysis, including anthropometric data, clinical fractures, and morphometric vertebral fractures (MVFs) assessed by X-rays. The prevalence of previous MVFs was 32.7% and 21.8% in the OB and NW groups, respectively (p < 0.05). All incident fractures and incident MVFs accounted for 10.7 and 6.3% among all participants within five years. Overweight/obesity and increase in weight or BMI during the follow-up had no associations with all incident fractures, incident MVFs, and incident clinical non-VFs among all participants. However, after multivariate adjustment, the increased BMI at baseline was the risk factor of incident MVFs in the OW group (odds ratio, OR 2.06, 95% confidence interval, 95% CI 1.16-3.66, p = 0.014), and increase in weight (OR 0.89, 95% CI 0.79-0.99, p = 0.036) or BMI (OR 0.77, 95% CI 0.59-0.99, p = 0.045) during the follow-up were the protective factors of all incident fractures in the NW group. Overweight/obesity and change in weight or BMI do not correlate with fracture risk in postmenopausal women, but an increase in weight is the protective factor against incident fractures in normal-weight participants. Overweight postmenopausal women with a higher BMI should pay attention to the risk of MVFs.

Incident vertebral fracture and longitudinal BMD change in Chinese postmenopausal women with early CKD: Peking Vertebral Fracture Study.

Early chronic kidney disease (CKD) and non-CKD individuals had similar morphometric vertebral fracture (mVF) incidence and longitudinal bone mineral density (BMD) change. CKD did not modify the association between BMD and incident mVF status. Patients with a higher baseline BMD had a higher longitudinal BMD loss in early CKD. PURPOSE: The aim of this 5-year longitudinal cohort study was to compare the risk of incident morphometric vertebral fracture (mVF) and longitudinal bone mineral density (BMD) change between individuals with early chronic kidney disease (CKD) and those without CKD. METHODS: A total of 869 Chinese postmenopausal women were enrolled in the study. Serum creatinine levels were assessed using standard methods, and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident mVF was confirmed through lateral radiographs of the thoracolumbar spine. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured using dual-energy X-ray absorptiometry. CKD was defined based on eGFR values: 60-89 mL/min/1.73m2 for stage 2 (n = 511) and 30-59 mL/min/1.73m2 for stage 3 (n = 92). The non-CKD group included individuals with an eGFR greater than or equal to 90 mL/min/1.73m2. RESULTS: The incidence of mVF was not statistically different between individuals with early CKD and those without CKD (4.1% in non-CKD, 6.3% in CKD stage 2, and 7.6% in CKD stage 3; p = 0.348). Neither eGFR nor CKD status was significantly associated with incident mVF in the multivariate logistic regression analysis. Baseline BMD T-scores were negatively associated with incident mVF (LS T-score, OR = 0.603, 95% CI = 0.468-0.777; FN T-score, OR = 0.511, 95% CI = 0.350-0.746). No evidence of interaction between BMD T-scores and CKD status were identified (p = 0.284-0.785) . The differences in longitudinal BMD changes between non-CKD and CKD groups were comparable (FN BMD: -6.31 ± 7.20% in non-CKD, -5.07 ± 8.20% in CKD stage 2, and -4.49 ± 8.40% in CKD stage 3, p = 0.556; LS BMD: -1.38 ± 8.18% in non-CKD, -0.32 ± 7.14% in CKD stage 2, and 1.5 ± 6.97% in CKD stage 3, p = 0.406). Individuals with a higher baseline FN BMD showed a greater longitudinal FN BMD loss (r = -0.185, p < 0.001) . CONCLUSIONS: Our study revealed that early CKD was not associated with an increased risk of incident mVF or greater longitudinal BMD loss. Moreover, CKD did not modify the association between BMD and the risk of incident mVF, suggesting that the management and prevention of fractures in early CKD should be approached similarly to those without CKD. Measurement of BMD appears to be crucial for predicting incident mVF risk and longitudinal bone loss in early CKD.

Misdiagnosed psychiatric manifestations in a rare disease: a case report of secondary anxiety syndrome in Cushing's disease.

Diagnosing and treating secondary psychiatric symptoms with accuracy can be challenging in clinical settings. In this case study, we report on a female patient with Cushing's disease who was misdiagnosed with anxiety disorder during her first psychiatric visit. Following initial ineffective psychiatric intervention, unexplained hypokalemia, and hypothyroidism, the patient visited the endocrinology clinic and was diagnosed with Cushing's disease. During the medical and surgical procedures that followed, high doses of psychotropic medication were continued to treat persisting anxiety. After discharge, the patient developed autonomic dysfunction and impaired consciousness. Upon readmission, serotonin syndrome due to inappropriate psychiatric medication was diagnosed. The management of secondary psychiatric syndromes must be adapted to changes in the patient's primary condition, which necessitates interdisciplinary collaboration in general hospital settings.

Shift in Calcium From Peripheral Bone to Axial Bone After Tumor Resection in Patients With Tumor-Induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. After successful tumor resection, patients can recover from hypophosphatemia quicky. However, data on the changes in bone mineral density (BMD) and microstructure in the short term after surgery remained unclear. OBJECTIVE: This work aimed to investigate the postoperative changes in BMD and microstructure both in peripheral and axial bone in TIO patients. METHODS: We evaluated BMD and microarchitecture in 22 TIO patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy x-ray absorptiometry (DXA) before and 3 months after surgery in this retrospective study. RESULTS: In this study, a total of 22 TIO patients who had recovered serum phosphate levels postoperatively were enrolled. After surgery, areal BMD (aBMD) increased by 21.6% in the femoral neck, by 18.9% in the total hip, and by 29.5% in the lumbar spine. Moreover, TBS increased by 14.1% (all P < .001). In contrast, trabecular or cortical volumetric BMD (vBMD), and microstructure of trabecular bone (trabecular number, separation and bone volume ratio) and cortical bone (cortical thickness and porosity) at the distal radius or tibia were further deteriorated. Correlation analyses found that changes in femoral neck and total hip aBMD were both conversely associated with changes in trabecular vBMD and bone volume ratio, while positively correlated with change in trabecular separation at the distal radius. CONCLUSION: Although aBMD and microstructure in the axial bone were improved, vBMD and microstructure in the peripheral bone were further impaired shortly after surgery. Correlation of improvement of aBMD in the total hip and femoral neck with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone in the short term after tumor resection in TIO patients.

A Chinese case of CHST3-related skeletal dysplasia and a systematic review.

PURPOSE: We reported a case with carbohydrate sulfotransferase 3 (CHST3) spondyloepiphyseal dysplasia and made a systematic review of all previously reported cases. METHODS: A 14.8-year-old boy underwent clinical, radiological, and genetic evaluations. The patients and five age-matched healthy boys accepted high-resolution peripheral quantitative computed tomography evaluation. All CHST3-related skeletal dysplasia cases from PubMed and Embase were collected and summarized. The genotype-phenotype correlation was analyzed. RESULTS: The proband complained of aggravated joint pain and had a compression fracture of L2 during his second decade. Physical examination showed a height Z score of -4.94, short limbs, and restricted movement of the elbows and knees. X-rays showed carpal epiphyseal dysplasia, enlargement of elbow and knee joints, and subluxation of the left hip. Echocardiography showed abnormal cardiac valves. Compared with the norm, his total and trabecular volumetric bone mineral density (BMD), and the microarchitecture of the trabecular bone had trends to be worse at the distal radius and tibia. Two novel missense variants of c.1343T>G and c.761C>G in CHST3 were inherited from his father and mother, respectively. In the systematic review, short stature, limited joint extension, joint pain, and joint dislocation were the most common characteristics of this disorder. Height Z score and the proportion of hearing impairment had no significant differences between the missense and nonmissense mutations groups. CONCLUSION: Progressive joint pain and movement restriction are the main characteristics of CHST3-related skeletal dysplasia. BMD and bone microarchitecture of this disorder needs further exploration. There is no apparent genotype-phenotype correlation in this disorder.

Association of early-life famine exposure with low bone mass in adulthood.

Famine exposure in early life has been found to have a long-term effect on metabolic diseases, but its effect on bone health was not clear. In this study, we found women, who suffered from famine exposure during their childhood or adolescence period, had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. The risk of clinical fracture was also elevated in adolescence-exposed women. PURPOSE: To investigate the correlation between famine exposure at certain stages and bone mass in adulthood. METHODS: We enrolled participants born in 1943-1962 from the China Osteoporosis Prevalence Study (COPS), which were classified into three famine exposure groups according to their birth year: fetal-famine exposure (1959-1962, n = 1693), childhood-famine exposure (1949-1958, n = 5557), and adolescence-famine exposure (1943-1948, n = 1530). We also selected age-balanced non-exposed participants as the control groups for men and women separately. Bone mineral density (BMD) and vertebral fractures (VFs) were measured by dual X-ray absorptiometry (DXA) and X-ray, respectively. The associations of famine exposure in early life with BMD were assessed via multiple linear regression. Logistic regression was performed to examine the association of famine exposure in early life with fracture risk with adjustments for covariates. RESULTS: In women, the childhood-exposed and adolescence-exposed groups had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. No significant decreased BMD was found in the fetal-exposed groups compared to the non-exposed groups in both sexes. Multiple linear regression analysis showed that famine exposure during childhood and adolescence was negatively associated with BMD at the femoral neck after adjusting for covariates in women. The risk of clinical fracture was also elevated in adolescence-exposed women. CONCLUSION: Famine exposure during early life especially childhood and adolescence is associated with decreased bone mass in adulthood in women but did not affect bone mass in men.

Ultra-High Performance Liquid Chromatography-Mass Spectrometry-based Serum Metabolomics for Early Diagnosis of Refractory Tumor-induced Osteomalacia: A Case-control Study.

CONTEXT: Nearly 20% patients with tumor-induced osteomalacia (TIO) experienced recurrence or nonrecovery after surgery. Serum fibroblast growth factor 23 and phosphate concentrations are not sufficient for prognosis in such cases. Despite its importance for understanding of prognosis and underlying pathogenesis, the alteration of systemic metabolism in refractory TIO remains unclear. OBJECTIVE: We aimed to find the metabolomic characteristics of refractory TIO and establish a novel predictive model for early discriminating refractory TIO based on their serum metabolomics. DESIGN AND SETTING: Cross-section study for comparison of metabolomic profile between TIO and normal control and longitudinal study for identifying prognostic model. METHODS: Based on liquid chromatography-tandem mass spectrometry, we analyzed the global metabolomes of preoperative sera from 86 samples (32 TIO recovery patients, 11 nonremission patients, and 43 matched controls). Statistical analyses, pathway enrichment, and receiver operating characteristic analysis were performed to identified and evaluate potential markers. RESULTS: Sparse partial least squares discriminant analysis indicated a clear separation of metabolomic profiles between healthy controls (HC) and TIO patients. The serum metabolites altered in different prognostic groups. L-pipecolic acid, 2-dodecylbenzenesulfonic acid, and 2-deoxygalactopyranose were the top 3 metabolites that were significantly perturbed. A combination of L-pipecolic acid and 2-dodecylbenzenesulfonic acid demonstrated a high-performance panel for TIO prognosis evaluated by random forest algorithm (area under the curve = 0.921, 95% CI, 0.787-0.995). CONCLUSIONS: We investigate the global metabolomes of refractory TIO and identify potential prognostic biomarkers preliminarily. A high sensitivity and specificity panel were identified as promising discriminating predictors, which need to be verified in more patients. This work may demonstrate novel insights into TIO prognosis and pathogenesis.

Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented. OBJECTIVES: To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study enrolled 202 patients with TIO. MAIN OUTCOME MEASUREMENTS: Occurrence of HPT in patients with TIO. RESULTS: HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels. CONCLUSIONS: HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.

Tumor-induced osteomalacia combined with acromegaly: A case report.

Both acromegaly and tumor-induced osteomalacia (TIO) are rare diseases caused by an excess hormone secreted by neuroendocrine neoplasms, which are growth hormone (GH) and fibroblast growth factor 23 (FGF23), respectively. GH elevates phosphate reabsorption via the effect of insulin-like factor 1 (IGF-1), while FGF23 inhibits phosphate reabsorption and reduces serum phosphate level markedly. A patient who developed a typical acromegaly appearance but was accompanied with height loss and hypophosphatemia for 2 years visited our hospital. Laboratory investigations showed GH and IGF-1 hypersecretion, as well as hypophosphatemia caused by renal phosphate wasting. Magnetic resonance image revealed a pituitary somatotroph adenoma. Octreoscan scintigraphy also found a causative tumor on the right foot for hypophosphatemia. Then, he underwent resection of the tumor on the right foot. His serum phosphate returned to normal immediately but elevated gradually. Then, we removed the pituitary adenoma of the patient, and the GH and phosphate levels returned to the normal range. Here, we report the first case with acromegaly combined with TIO, the changing process of his phosphate concentration suggests an interesting concurrent effect of excess GH and FGF23 in this rare condition.

Improvement of Bone Health and Initiation of Puberty Development in Camurati-Engelmann Disease With Glucocorticoid and Losartan Treatment: A Case Report and Review of Literature.

Camurati-Engelmann Disease (CED) is a rare sclerosing bone disease, sometimes associated delayed puberty. The treatment effect of glucocorticoid and angiotensin II receptor blocker (ARB) in bone health and puberty development remain unclear. We report a case of an 18-year-old girl who presented for a history of an enlarged head, pain of lower limbs, and no menstrual onset or breast development. Radiographs revealed thickening of skull and cortices in the diaphysis but sparse bone trabeculae in the spine and metaphysis. Sanger sequencing detected a mutation of c. 652C>T (p. R218C) in the gene TGFB1 and confirmed the diagnosis of CED. After treatment of a medium-to-small dosage of prednisone and losartan for 28 months, we observed improvement of bone mass in spine and hip and body fat mass and found initiation of puberty development. By a systemic review of current treatment strategies in patients with CED, we found that most cases reported relief of bone pain with treatment of glucocorticoid or ARB, but none has reported the outcome of hypogonadotropic hypogonadism. We propose that long-term use of glucocorticoid combined with ARB may inhibit the activation of TGFß1 in CED, improve adipogenesis, and thus initiate puberty development and improve the bone mass in spine and hip.

Bone Volumetric Density, Microarchitecture, and Estimated Bone Strength in Tumor-Induced Rickets/Osteomalacia Versus X-linked Hypophosphatemia in Chinese Adolescents.

Tumor-induced rickets/osteomalacia (TIR/O) severely impairs bone microarchitecture and bone strength. However, no study has described the microarchitectural quality of bone in adolescent patients with TIR/O. TIR/O affects bone quality more severely than the inherited causes of hypophosphatemia, the most common form of which is X-linked hypophosphatemia (XLH). Nevertheless, differences of the microarchitectural quality of the bone between TIR/O and XLH have never been clarified. Therefore, in this study, we used high-resolution peripheral quantitative computed tomography to assess bone microarchitecture in five Chinese adolescent TIR/O patients, and these were compared with 15 age- and gender-matched XLH patients as well as 15 age- and gender-matched healthy controls. Compared with the healthy controls, the TIR/O patients presented with significantly lower volumetric bone mineral densities (vBMDs), severely affected bone microarchitecture, and profoundly weaker bone strength. The distal tibia was more severely affected than the distal radius. Compared with the XLH patients, the TIR/O patients showed deteriorated bone quality notably at the distal tibia and in the cancellous compartment, reflected by 45.9% lower trabecular vBMD (p = 0.029), 40.2% lower trabecular fraction (p = 0.020), 40.6% weaker stiffness (p = 0.058), and 42.7% weaker failure load (p = 0.039) at the distal tibia. The correlation analysis showed that a higher level of serum FGF23 and a lower level of serum phosphate were associated with a poorer bone microarchitecture and a weaker estimated bone strength in the hypophosphatemic patients of our study. In conclusion, our study demonstrated significantly lower vBMDs, severely impaired bone microarchitecture, and profoundly weaker bone strength in Chinese adolescent patients with TIR/O, notably at the distal tibia, compared with the same parameters in age- and sex-matched healthy controls and XLH patients, which was possibly caused by excessive FGF23 production and secretion, chronically severe hypophosphatemia, and weak mechanical stimulus at the lower extremities. These findings further our understanding of the impact of different kinds of hypophosphatemic rickets/osteomalacia on bone quality.

Overview of the clinical efficacy and safety of eldecalcitol for the treatment of osteoporosis.

Eldecalcitol (ELD) is a new oral analog of the active form of vitamin D with anti-resorptive properties. We conducted a meta-analysis to investigate the efficacy and safety of ELD in osteoporosis. Compared with alfacalcidol, ELD significantly lowered vertebral facture risk, increased bone mineral density, but also had a higher risk of hypercalciuria. PURPOSE: This study aimed to investigate the efficacy and safety of eldecalcitol (ELD) in osteoporosis by examining fracture rates, bone mineral density (BMD), bone turnover markers, and adverse events as outcomes. METHODS: PubMed, EMBASE, and Cochrane Library were searched up to July 20, 2020, to identify eligible randomized controlled trials. The odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval was calculated by the random-effects model. RESULTS: ELD significantly increased lumbar BMD (WMD: 2.80; 95% CI: 1.60, 4.00; P < 0.001, 2 studies involved), total hip BMD (WMD: 2.11; 95% CI: 0.68, 3.55; P = 0.004, 2 studies involved), and femoral neck BMD (WMD: 1.78; 95% CI: 0.76, 2.79; P = 0.001, 1 study involved) compared with alfacalcidol. Moreover, ELD caused a significantly lower rate of vertebral fracture (OR: 0.52; 95% CI: 0.29-0.95; P = 0.034, 2 studies involved) than alfacalcidol, but did not lower the rate of non-vertebral facture (OR: 0.44; 95% CI: 0.06-3.05; P = 0.405, 2 studies involved) compared with alfacalcidol. ELD significantly reduced the percentage change in bone-specific alkaline phosphatase (WMD: - 15.40; 95% CI: - 20.30, - 10.60; P < 0.001, 1 study involved) and serum type I collagen C-telopeptide (WMD: - 38.50; 95% CI: - 50.00, - 27.10; P < 0.001, 1 study involved) as compared with alfacalcidol. ELD was also associated with higher risk of hypercalciuria compared with alfacalcidol (OR: 1.64; 95% CI: 1.22, 2.20; P = 0.001, 2 studies involved). CONCLUSIONS: This systematic review indicated that ELD was superior than alfacalcidol for improving vertebral fracture risk and BMD. Further large-scale trials should be conducted to verify the long-term effects and safety of ELD in osteoporosis. PROSPERO REGISTRATION NUMBER: CRD42020147518.

Avoiding Misdiagnosis and Missed Diagnosis for Appropriately Treating Spinal Osteoid Osteomas: A Single-Center Experience.

OBJECTIVES: To analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma, and to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients. METHODS: We performed a retrospective cohort study on patients with spinal osteoid osteoma in Beijing Jishuitan Hospital from January 1983 to September 2019. All patients underwent surgery. The outcome measures were the extent of local pain, nocturnal pain, radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery. RESULTS: Thirty-seven patients with spinal osteoid osteoma were recruited in the study. A total of 27% were female, and the mean (SD) age at diagnosis was 21.3 (8.7) years. A total of 87.0% of patients presented with nocturnal pain, and 94.7% of patients were responsive to NSAIDS treatment. The mean (SD) time from the initial onset of symptoms to the final diagnosis was 14.7 (12.5) months. Only four of 37 (10.8%) patients were correctly diagnosed with spinal osteoid osteoma on the first visit to the local hospital. CT is associated with a higher diagnosis rate than X-ray or MRI on the first visit. Surgical navigation was used in 88.9% of patients who underwent curettage resection, and in 10% of patients who underwent en bloc resection. A total of 37 of 37 patients (100%) reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow-ups. CONCLUSIONS: Spinal CTs are recommended to be performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment, to avoid misdiagnosis and missed diagnosis of spinal osteoid osteoma.

Alteration of Bone Density, Microarchitecture, and Strength in Patients with Camurati-Engelmann Disease: Assessed by HR-pQCT.

Camurati-Engelmann disease (CED) is a rare autosomal-dominant skeletal dysplasia caused by mutations in the transforming growth factor-ß1 (TGFB1) gene. In this study, a retrospective review of patients with CED evaluated at Peking Union Medical College Hospital in Beijing, China, between November 30, 2000 and November 30, 2020 was conducted. Data including demographic data, manifestations, and examination results were characterized. Furthermore, bone geometry, density, and microarchitecture were assessed and bone strength was estimated by HR-pQCT. Results showed the median age at onset was 2.5 years. Common manifestations included pain in the lower limbs (94%, 17/18), abnormal gait (89%, 16/18), genu valgum (89%, 16/18), reduced subcutaneous fat (78%, 14/18), delayed puberty (73%, 8/11), muscle weakness (67%, 12/18), hearing loss (39%, 7/18), hepatosplenomegaly (39%, 7/18), exophthalmos or impaired vision or visual field defect (33%, 6/18), and anemia (33%, 7/18). Twenty-five percent (4/16) of patients had short stature. Serum level of alkaline phosphatase was elevated in 41% (7/17) of patients whereas beta-C-terminal telopeptide was elevated in 91% of patients (10/11). Among 12 patients, the Z-scores of two patients were greater than 2.5 at the femur neck and the Z-scores of five patients were lower than -2.5 at the femur neck and/or lumbar spine. HR-pQCT results showed lower volumetric BMD (vBMD), altered bone microstructure and lower estimated bone strength at the distal radius and tibia in patients with CED compared with controls. In addition, total volume bone mineral density and cortical volumetric bone mineral density at the radius were negatively correlated with age in patients with CED, but positively correlated with age in controls. In conclusion, the largest case series of CED with characterized clinical features in a Chinese population was reported here. In addition, HR-pQCT was used to investigate bone microstructure at the distal radius and tibia in nine patients with CED, and the alteration of bone density, microstructure, and strength was shown for the first time. © 2021 American Society for Bone and Mineral Research (ASBMR).

Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among women in China: a simulation projection model from 2020 to 2040.

Annual osteoporotic fractures is projected to increase by 135% from 6.9 M (2020) to 16.2 M (2040), increasing the economic burden by 121% from $29.9B (2020) to $65.9B (2040). INTRODUCTION: Globally, aging populations drive significant increases in osteoporosis prevalence. In China, the number of women aged ≥ 65 years is expected to more than double from 2020 (91.5 M) to 2040 (183.6 M). Using a microsimulation model, impact of increased diagnosis and treatment of postmenopausal women (PMW) with osteoporosis on anticipated reduction in fractures and associated costs in China from 2020 to 2040 was projected. METHODS: A microsimulation model was developed to project annual incidence and costs of osteoporotic fractures among PMW in China from 2020 to 2040. Fracture risk was estimated using the simplified Fracture Risk Assessment Tool (FRAX). Fractures estimates were based on annualized FRAX risk and impact of treatment. Published literature informed inputs for direct and indirect fracture costs, DXA screening costs, and treatment costs and efficacy. China's current screening and treatment rates were compared against 50% increases to (i) case finding (screening rate and subsequent treatment rate) and (ii) treatment rate among those at highest fracture risk. RESULTS: From 2020 to 2040, 241.7 M osteoporotic fractures are projected to cost $997B. Increased treatment scenario prevented 24.6 M fractures and saved $56B. Increased case finding scenario prevented 26 M fractures and saved $61.7B. CONCLUSION: Osteoporosis underdiagnosis and undertreatment among the aging Chinese population will considerably burden patients, caregivers, and society. Policy changes to increase screening and treatment rates may result in significant cost savings and clinical benefits.

Prevalence of Osteoporosis and Fracture in China: The China Osteoporosis Prevalence Study.

Importance: The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known. Objective: To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China. Design, Setting. and Participants: This cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate. Main Outcomes and Measures: Weighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography. Results: A total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture. Conclusions and Relevance: In this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.