Denosumab, a novel agent that inhibits osteoclasts, reduces the risk of fracture in patients with osteoporosis. However, worsening of hypophosphatemia and other symptoms may be induced by denosumab in patients with pre-existing hypophosphatemic osteomalacia. A 58-year-old man with hepatitis B presented with diffuse bone pain and muscle weakness. Denosumab was prescribed by the orthopedist according to documented low bone mass and spine compression fracture. After administering denosumab, the patient's bone pain worsened, and he later developed a right tibia stress fracture. His condition was diagnosed as adult-onset hypophosphatemic osteomalacia complicated by multiple bone fractures, which resulted from Fanconi syndrome with proximal tubulopathy due to tenofovir disoproxil fumarate (TDF) treatment for his hepatitis B. Denosumab use leads to aggressive hypophosphatemic osteomalacia and the complication of stress fractures, because of its effects on bone resorption. Physicians should be aware that in patients with chronic hepatitis B monoinfection who are administered TDF therapy, bone pain or fracture is possible but preventable by timely monitoring of serum phosphate levels. Denosumab should not be used in patients with untreated osteomalacia or vitamin D deficiency, as it may lead not only to hypocalcemia but also to hypophosphatemia in these patients.
BackgroundObesity is a major risk factor for diabetes mellitus (DM), which is in turn a major risk factor for cardiovascular diseases such as coronary artery disease and stroke. As few studies have investigated sex differences in the association between obesity and incidence of DM, the aim of this longitudinal study was to explore this issue in a large group of Taiwanese participants.MethodsA total of 24,346 participants were enrolled in this study, of whom 8,334 (mean age, 50.6 ± 11.0 years) were male and 16,012 (mean age, 50.5 ± 10.1 years) were female. The following obesity-related indices were studied: body mass index, waist-to-height ratio, waist-to-hip ratio (WHR), body roundness index, conicity index (CI), body adiposity index, abdominal volume index, lipid accumulation product (LAP), and visceral adiposity index (VAI).ResultsThe analysis showed significant associations between all of these indices with incidence of DM (all p < 0.001). In the male participants, the strongest predictors for incidence of DM were LAP (AUC = 0.692), WHtR (AUC = 0.684), and WHR (AUC = 0.683). In the female participants, the strongest predictors were LAP (AUC = 0.744), WHtR (AUC = 0.710) and VAI (AUC = 0.710), followed by BRI (AUC = 0.708).ConclusionStrong associations were found between the studied obesity-related indices and incidence of DM, and sex differences were found. Hence, to better control DM, reducing body weight may be beneficial in addition to lifestyle modifications, diet control, and pharmacological interventions.
The global prevalence and incidence of chronic kidney disease (CKD) continue to increase. Whether hyperuricemia is an independent risk factor for renal progression and whether there are sex differences in the relationships between serum uric acid (UA) and a decline in renal function are unclear. Therefore, in this longitudinal study, we aimed to explore these relationships in a large cohort of around 27,000 Taiwanese participants in the Taiwan Biobank (TWB), and also to identify serum UA cutoff levels in men and women to predict new-onset CKD. A total of 26,942 participants with a median 4 years of complete follow-up data were enrolled from the TWB. We excluded those with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) at baseline (n = 297), and the remaining 26,645 participants (males: 9356; females: 17,289) were analyzed. The participants who developed CKD during follow-up were defined as having incident new-onset CKD, and those with a serum UA level >7 mg/dL in males and >6 mg/dL in females were classified as having hyperuricemia. After multivariable analysis, hyperuricemia (odds ratio [OR], 2.541; 95% confidence interval [CI], 1.970–3.276; p < 0.001) was significantly associated with new-onset CKD. Furthermore, in the male participants (n = 9356), hyperuricemia (OR, 1.989; 95% CI, 1.440–2.747; p < 0.001), and quartile 4 of UA (vs. quartile 1; OR, 2.279; 95% CI, 1.464–3.547; p < 0.001) were significantly associated with new-onset CKD, while in the female participants (n = 17,289), hyperuricemia (OR, 3.813; 95% CI, 2.500–5.815; p < 0.001), quartile 3 of UA (vs. quartile 1; OR, 3.741; 95% CI, 1.250–11.915; p = 0.018), and quartile 4 of UA (vs. quartile 1; OR, 12.114; 95% CI, 14.278–34.305; p < 0.001) were significantly associated with new-onset CKD. There were significant interactions between hyperuricemia and sex (p = 0.024), and quartiles of serum UA and sex (p = 0.010) on new-onset CKD. Hyperuricemia was associated with new-onset CKD in the enrolled participants, and the interactions between hyperuricemia and sex were statistically significant. Hyperuricemia was more strongly associated with new-onset CKD in the women than in the men.
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