Deep-Learning-Based Detection of Vertebral Fracture and Osteoporosis Using Lateral Spine X-Ray Radiography.

Osteoporosis and vertebral fractures (VFs) remain underdiagnosed. The addition of deep learning methods to lateral spine radiography (a simple, widely available, low-cost test) can potentially solve this problem. In this study, we develop deep learning scores to detect osteoporosis and VF based on lateral spine radiography and investigate whether their use can improve referral of high-risk individuals to bone-density testing. The derivation cohort consisted of patients aged 50 years or older who underwent lateral spine radiography in Severance Hospital, Korea, from January 2007 to December 2018, providing a total of 26,299 lateral spine plain X-rays for 9276 patients (VF prevalence, 18.6%; osteoporosis prevalence, 40.3%). Two individual deep convolutional neural network scores to detect prevalent VF (VERTE-X pVF score) and osteoporosis (VERTE-X osteo score) were tested on an internal test set (20% hold-out set) and external test set (another hospital cohort [Yongin], 395 patients). VERTE-X pVF, osteo scores, and clinical models to detect prevalent VF or osteoporosis were compared in terms of the areas under the receiver-operating-characteristics curves (AUROCs). Net reclassification improvement (NRI) was calculated when using deep-learning scores to supplement clinical indications for classification of high-risk individuals to dual-energy X-ray absorptiometry (DXA) testing. VERTE-X pVF and osteo scores outperformed clinical models in both the internal (AUROC: VF, 0.93 versus 0.78; osteoporosis, 0.85 versus 0.79) and external (VF, 0.92 versus 0.79; osteoporosis, 0.83 versus 0.65; p < 0.01 for all) test sets. VERTE-X pVF and osteo scores improved the reclassification of individuals with osteoporosis to the DXA testing group when applied together with the clinical indications for DXA testing in both the internal (NRI 0.10) and external (NRI 0.14, p < 0.001 for all) test sets. The proposed method could detect prevalent VFs and osteoporosis, and it improved referral of individuals at high risk of fracture to DXA testing more than clinical indications alone. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Analysis of the cause and management of persistent laboratory abnormalities occurring after the surgical treatment of primary hyperparathyroidism.

Purpose: The surgical success rate for primary hyperparathyroidism (PHPT) is currently 95%-98%. However, 3%-24% of patients show persistently elevated (Pe) parathyroid hormone (PTH) levels after parathyroidectomy (PTX). This single-center retrospective study aimed to compare the outcomes of patients with normal PTH and PePTH levels after successful PTX and to identify the factors associated with PePTH. Methods: The normal group, defined as patients with normal serum calcium and PTH levels immediately after PTX, was compared with the PePTH group (patients with normal or low serum calcium and increased serum PTH levels up to 6 months postoperatively) to determine the causes of disease in the PePTH group. Results: There were no significant differences in age, sex, or preoperative estimated glomerular filtration rate between the normal PTH group (333 of 364, 91.5%) and the PePTH group (31 of 364, 8.5%). However, there were significant differences in preoperative 25-hydroxyvitamin D (17.9 and 11.8 ng/mL, respectively; P = 0.003) and PTH levels (125.5 and 212.4 pg/mL, respectively; P < 0.001) between the 2 groups. Among the 31 cases of the PePTH group, 18 were attributed to vitamin D deficiency. Conclusion: Preoperative vitamin D deficiency is a predictive factor for PePTH. Therefore, preoperative administration of vitamin D supplements may reduce the probability of postoperative disease persistence. Patients with temporary laboratory abnormalities within 6 months after successful PTX should be monitored, and appropriate vitamin D and calcium supplementation may reduce the effort and cost of various examinations or reoperations.

Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study.

AIMS: This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort. METHODS AND RESULTS: From a nationwide health screening database in South Korea, a total of 11 297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days [total calcium group; calcium supplementation only (CaO), n = 567; calcium supplementation in combination with vitamin D (CaD), n = 10 730] were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVDs) per 1000 person-years was not different between the groups: 9.73 in the total calcium group and 8.97 in the control group [adjusted hazard ratio (HR): 1.12; 95% confidence interval (CI): 0.99-1.28; P = 0.08]. However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17-2.04; P < 0.01), especially non-fatal myocardial infarction (HR: 1.89; 95% CI: 1.23-2.91; P < 0.01), compared with no calcium supplementation. CONCLUSION: Our population-based study supported that taking calcium supplementation combined with vitamin D did not appear to be harmful to cardiovascular health, but reminded that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.

Association between serum 25-hydroxyvitamin D concentrations and depressive symptoms in an older Korean population: A cross-sectional study.

BACKGROUND: This study aims to examine associations between serum 25-hydroxyvitamin D [25(OH)D] concentrations and depressive symptoms in an older Korean population. METHODS: The study used data from the Korean Urban Rural Elderly study, which enrolled 2942 participants aged 65 years or older from urban and rural communities. After excluding those treated with antidepressants, we conducted cross-sectional analysis of 2853 participants (962 men and 1891 women). Serum 25(OH)D was analyzed as both a continuous and categorized variable. Depressive symptoms were assessed using the Korean version of the Geriatric Depression Scale - Short Form. Multivariate logistic regression analyses were conducted to examine relationships between serum 25(OH)D and depressive symptoms for men and women separately. RESULTS: In men, ORs (95% CIs) for depressive symptoms were 1.74 (0.85, 3.58), 2.50 (1.20, 5.18), and 2.81 (1.15, 6.83) for those with a 25(OH)D concentration of 20.0-29.9, 10.0-19.9, and <10.0ng/mL, respectively (P-trend=0.013), compared with those with a 25(OH)D concentration of ≥30.0ng/mL, after adjustment for study year, month of assay, age, parathyroid hormone, body mass index, number of comorbidities, smoking status, alcohol intake, exercise, sleep duration, income, education, cohabitation status, and residential area. In women, the associations between 25(OH)D and depressive symptoms were significant neither before nor after adjustment. LIMITATIONS: Due to the cross-sectional study design, causal association is uncertain. Intake of vitamin D supplements and outdoor activity were not examined. CONCLUSIONS: Our findings suggest that lower concentrations of vitamin D are independently associated with depressive symptoms in older Korean adults.

Efficacy of a combined alendronate and calcitriol agent (Maxmarvil®) in Korean postmenopausal women with early breast cancer receiving aromatase inhibitor: a double-blind, randomized, placebo-controlled study.

The use of aromatase inhibitor (AI) in postmenopausal women with hormone receptor (HR)-positive early breast cancer (EBC) produces a deleterious effect on bone mass and an increase in fractures. Several studies using intravenous bisphosphonates have shown effective management of AI-induced bone loss. To determine whether a lower dosage in oral form combined with calcitriol can effectively manage AI-induced bone loss, we performed a randomized, double-blind, prospective, placebo-controlled 24-week trial with a combination of alendronate and 0.5-µg of calcitriol daily to HR-positive EBC patients. A total of 98 Korean postmenopausal women with HR-positive EBC who received daily AI, calcium and vitamin D were randomly assigned to 5-mg of alendronate and 0.5-µg of calcitriol (Maxmarvil®) or placebo groups. The bone mineral density (BMD) and turnover markers were measured. At week 24, the difference in lumbar BMD between the groups was 3.0% (p < 0.005). The increase in C-telopeptide after 24 weeks was significantly less in the Maxmarvil group compared to that in the placebo group (35.2 ± 17.5% vs. 109.8 ± 28.6%, p < 0.05). Our study demonstrates that a combination of 5-mg alendronate and 0.5-µg calcitriol is effective to prevent bone loss due to AI in Korean postmenopausal women with EBC.

Effect of teriparatide on pregnancy and lactation-associated osteoporosis with multiple vertebral fractures.

Pregnancy and lactation-associated osteoporosis (PLO) is very rare, but it can cause severe vertebral compression fractures with disabling back pain. PLO patients have commonly been treated with antiresorptive agents against high bone turnover. There are, however, some concerns regarding the use of bisphosphonates: (1) PLO occurs during the first pregnancy with a high possibility of recurrence during the second pregnancy, (2) long-term outcomes of bisphosphonates in PLO are lacking, and (3) there is a possibility of bisphosphonates accumulated in the bones crossing the placenta. Therefore, alternative therapies must be considered. We analyzed the effect of teriparatide (TPTD), the human recombinant parathyroid hormone (1-34), for 18 months in three women with PLO. Multiple vertebral fractures with severe back pain appeared within 6 months after their first childbirth. Two of them had a family history of osteoporosis. Lactation was discontinued immediately after diagnosis of PLO. Calcium carbonate, cholecalciferol, and TPTD were prescribed. The back pain immediately resolved. Bone mineral density (BMD) increased by 14.5-25.0% (mean 19.5%) at the lumbar spine and by 9.5-16.7% (mean 13.1%) at the femoral neck, after 18 months of treatment. The final Z scores in these PLO patients were nearly normalized. Two women had a second baby without any complication. BMD significantly improved after 18 months of treatment with TPTD without further fractures. In conclusion, TPTD should be considered to avoid long-term morbidity in young patients with PLO and is highly encouraged for use in PLO patients with multiple vertebral fractures.

Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732.

The systemic treatment with angiogenesis inhibitor has been shown to result in weight reduction and adipose tissue loss in various models of obesity. To verify the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732's peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.) in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates. Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion (CTA) was performed using lithium chloride (LiCl) as a positive control agent in Long-Evans Tokushima Otsuka and Otsuka Long-Evans Tokushima fatty (OLETF) rats. As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake and the body weight significantly in both treated obese (e.g. 114.8 +/- 13.4 g vs 170.7 +/- 20.6 g, 7.9 +/- 0.5% decrease vs 0.3 +/- 2.2% decrease; in treated OLETF rat versus control OLETF rat, P < 0.01 respectively) and non-obese models. Epididymal and mesenteric fat pads, and the size of adipocytes were significantly decreased in treated rats. A single i.c.v. injection decreased food intake and body weight in ARC lesion mice and ob/ob mice but not in normal littermates. Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl injection, which is a commonly used agent to produce a CTA. In conclusion, CKD-732 causes significant body weight and appetite reduction, possibly by decreasing adiposity directly and inducing central anorexia, which is partly explained by a CTA. These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug.