Teriparatide Associated Late Hypercalcemia: A Report of Two Cases and Literature Review.

Introduction: Teriparatide, recombinant human parathyroid hormone (1-34), is a safe and usually well-tolerated medication. We describe two cases of late-onset hypercalcemia associated with teriparatide use and report current evidence of hypercalcemia during the treatment with PTH analogs. Case report: Case 1 is a 54-year-old man with a history of osteoporosis, previously treated with 6 months of teriparatide, but had not been consistent in taking the medication. Before restarting teriparatide, his serum calcium, PTH and vitamin D were normal. Six months into the treatment, he developed asymptomatic hypercalcemia of 11.2 mg/dL 24 h after the last dose. Repeat serum calcium was normal and treatment was continued. Case 2 is a 75-year old woman with a history of osteopenia and severe scoliosis. Before starting teriparatide, her calcium, PTH and vitamin D were normal. Six months into the treatment, she developed asymptomatic hypercalcemia of 12.5 mg/dL. Teriparatide was held and subsequently her serum calcium normalized. Discussion: Transient hypercalcemia can occur during treatment with teriparatide and usually resolves within 16 h after administration. Late hypercalcemia, occurring more than 24 h after the dose, is rarely seen. It is usually mild, asymptomatic and rarely occurs repeatedly. Hypercalcemia occurs more often in patients with pre-existing hypercalcemia or vitamin D deficiency. It is rarely a cause of treatment disruption (0.18-4%). Conclusion: Clinicians should be aware of this side effect, especially in patients who may be at risk of complications of hypercalcemia.

Evaluation of Glycemic Control and Predictors of Severe Illness and Death in Patients with Diabetes Hospitalized With COVID-19.

Objectives: To identify risk factors for severe disease and death among patients with diabetes and coronavirus disease 2019 (COVID-19) infection. Methods: This retrospective cohort study conducted at three hospitals included 733 consecutive patients with DM admitted with confirmed COVID-19 (March 1 - December 31, 2020). Multivariable logistic regression was performed to identify predictors of severe disease and death. Results: The mean age was 67.4 ± 14.3 years, 46.9% were males and 61.5% were African American. Among all patients, 116 (15.8%) died in the hospital. A total of 317 (43.2%) patients developed severe disease, 183 (25%) were admitted to an ICU and 118 (16.1%) required invasive mechanical ventilation. Increasing BMI (OR, 1.13; 95% CI, 1.02-1.25), history of chronic lung disease (OR, 1.49; 95% CI, 1.05-2.10) and increasing time since the last HbA1c test (OR, 1.25; 95% CI, 1.05-1.49) were the preadmission factors associated with increased odds of severe disease. Preadmission use of metformin (OR, 0.67; 95% CI, 0.47-0.95) or GLP-1 agonists (OR, 0.49; 95% CI, 0.27-0.87) was associated with decreased odds of severe disease. Increasing age (OR, 1.21; 95% CI, 1.09-1.34), co-existing chronic kidney disease greater than stage 3 (OR, 3.38; 95% CI, 1.67-6.84), ICU admission (OR, 2.93; 95% CI, 1.28-6.69) and use of invasive mechanical ventilation (OR, 8.67, 95% CI, 3.88-19.39) were independently associated with greater odds of in-hospital death. Conclusion: Several clinical characteristics were identified to be predictive of severe disease and in-hospital death among patients with underlying diabetes hospitalized with COVID-19.

Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women's Health Initiative Sight Exam ancillary study.

PURPOSE: To examine the association of cardiovascular disease (CVD), CVD risk factors, and CVD treatment with age-related macular degeneration (AMD). DESIGN: Observational analysis of a randomized clinical trial. SETTINGS: The Women's Health Initiative Sight Examination (WHISE), an ancillary study to the Women's Health Initiative's clinical trial of hormone replacement therapy. STUDY POPULATION: A total of 4,288 women age 63 years and older. OBSERVATION PROCEDURES: Information on CVD and its risk factors were obtained from a standardized questionnaire and examination. MAIN OUTCOME MEASURE: AMD as determined by standardized grading of fundus photographs. RESULTS: Prevalence of any AMD was 21.4% (n = 919). Of those with AMD, 5.8% (n = 53) had signs of exudative AMD (n = 39) or pure geographic atrophy (n = 14), limiting the power to examine associations. Significant associations between late AMD and CVD risk factors were (odds ratio [OR], 95% confidence interval [CI]) older age (1.19, 1.13 to 1.27, P < .0001), more pack years smoked (1.02 per pack-year smoked, 1.003 to 1.03, P = .01), systolic blood pressure (0.84 per 10 mm Hg, 0.71 to 0.995, P = .04), report of taking calcium channel blockers (2.49, 1.21 to 5.12, P = .04), self-reported history of diabetes (2.00, 1.01 to 3.96, P = .05), and greater body mass index (1.05 per 1 kg/m, 1.001 to 1.10, P = .05). History of myocardial infarction, stroke, use of statins, or white blood cell count was not associated with AMD. CONCLUSIONS: Results suggest that smoking, use of calcium channel blockers, diabetes, and obesity are risk factors for late AMD in women. However, the association of late AMD with systolic blood pressure and the effects of other CVD risk factors on early AMD need to be further explored.

Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative.

OBJECTIVE: Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo. METHODS: In an ancillary substudy of women randomized to calcium carbonate (1,000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) or placebo, nested within the Women's Health Initiative trial of estrogen among women who underwent hysterectomy, we measured CAC with cardiac CT in 754 women aged 50 to 59 years at randomization. Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment, and scans were read centrally. CAC scores were measured by a central reading center with masking to randomization assignments. RESULTS: Posttrial CAC measurements were similar in women randomized to calcium/D supplementation and those receiving placebo. The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo (rank test P value = 0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, > or =10, and > or =100) for calcium/D versus placebo were 0.92 (95% CI, 0.64-1.34), 1.29 (0.88-1.87), and 0.90 (0.56-1.44), respectively. Corresponding odds ratios among women with a 50% or higher adherence to study pills and for higher levels of CAC (>300) were similar. CONCLUSIONS: Treatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women. Whether higher or lower doses would affect this outcome remains uncertain.

Homocysteine levels and risk of hip fracture in postmenopausal women.

BACKGROUND: Recent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy. OBJECTIVE: The aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk. DESIGN: We conducted a case-control study in the Women's Health Initiative Observational Study, a study of postmenopausal women (n = 93,676) recruited in the United States. We selected 400 incident cases of hip fracture and 400 controls matched on age, ethnicity, and blood draw date among women not on osteoporosis therapies. Outcome measures included physician-adjudicated, incident hip fractures. Baseline lifestyle and nutritional questionnaires were performed. RESULTS: The risk of hip fracture increased 1.38-fold [95% confidence interval (CI), 1.14, 1.66] for each sd increase in serum homocysteine level after adjustment for fracture risk factors. This association was not affected by adjustment for dietary folate, B6, or B12 intake, but it diminished after adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66-1.79), a measure of renal function not affected by muscle mass. Among women in the highest quartile of homocysteine and cystatin-C compared to those without elevations in either biomarker, the risk of hip fracture was substantially elevated (odds ratio, 2.8; 95% CI, 1.61-4.87). CONCLUSIONS: This study indicates that high homocysteine levels are associated with an increased risk of hip fracture, which could be accounted for by poor renal function.