calcitriol and Hip-Fractures

Relationships between 1,25-dihydroxyvitamin D (1,25(OH)2 D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)2 D with bone mineral density (BMD), BMD change, and incident non-vertebral fractures in a cohort of older men and compared them with those of 25-hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual-energy X-ray absorptiometry (DXA) data (4.5 years of follow-up). A case-cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)2 D were tested for each outcome. Over an average follow-up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)2 D had lower baseline BMD. 1,25(OH)2 D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)2 D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19-3.33). Adjustment of 1,25(OH)2 D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)2 D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)2 D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)2 D. These results do not support the hypothesis that measures of 1,25(OH)2 D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.

Topics: Aged; Aged, 80 and over; Bone Density; Follow-Up Studies; Hip Fractures; Humans; Incidence; Male; Radiography; Risk Factors; Vitamin D

The OPG/RANKL/RANK system is important in the balance between bone formation and resorption. We used primary human osteoblasts (hOBs) cells to examine the impact of 17-beta-estradiol (E2) or/and 1,25-dihydroxyvitamin D (1,25D) in OPG/RANKL system in 28 post-menopausal (PM) women; (a) with hip fracture (OP) or (b) with osteoarthritis (OA). The hOB from OP patients proliferated slower during the first stage, than the OA women (31.5+/-2.6 and 21.4+/-1.3 days, respectively, p<0.05). The OP group secreted significantly higher OPG protein levels than the OA women (10.1+/-2.6 and 4.4+/-0.8pmol/L, respectively, p<0.05). The 1,25D and 1,25D+E2 induce an increase in RANKL and RANKL/OPG mRNA expression in OP patients above 200% (p<0.05). HOBs from the osteoporotic hip initially proliferate slower but after reaching the first cellular confluence, the proliferation rate is equal in both groups. Furthermore, hOBs from hips with OP present a higher protein secretion of OPG, and higher RANKL and RANKL/OPG expression ratio in response to 1,25D and 1,25D+E2, than hOBs from OA women. All this could suggest that the greater bone loss that characterizes OP patients can be mediated due to differences in the secretion and expression of the RANKL/OPG system in response to different stimuli.

Topics: Aged; Aged, 80 and over; Cells, Cultured; Estradiol; Female; Gene Expression Regulation; Hip Fractures; Humans; Osteoarthritis; Osteoblasts; Osteoporosis; Osteoprotegerin; Postmenopause; RANK Ligand; RNA, Messenger; Vitamin D

Incidence of hip fracture among patients with Alzheimer's disease (AD), especially in elderly patients, is high. To analyze risk factors of hip fracture, we prospectively studied a cohort of elderly female patients with AD. Subjects studied were 225 female patients with AD, and the average age was 76 years old. At baseline, we recorded body mass index (BMI), a score of Mini-Mental State Examination (MMSE) and bone mineral density (BMD), and measured serum concentrations of ionized calcium, intact parathyroid hormone (PTH), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), intact bone Gla protein (BGP), 25-hydroxyvitamin (25-OHD) and 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). The patients were followed for 2 years. During the 2-year study, hip fractures occurred in 29 patients. We compared baseline variables between the 29 patients with and 176 patients without hip fracture. AD patients with lower BMD, low concentrations of serum ionized calcium and 25-OHD (mean 3.0 ng/ml) with compensatory hyperparathyroidism were found to have an increased risk of hip fracture. Also, concentrations of serum ICTP and BGP were higher in the fracture group than in the nonfracture group. Elderly female AD patients with low BMD and serum 25-OHD concentrations <5 ng/ml with secondary hyperparathyroidism have a high risk of hip fracture, and the risk may be reduced by vitamin D supplementation.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Body Mass Index; Bone Density; Calcium; Collagen Type I; Demography; Female; Follow-Up Studies; Hip Fractures; Humans; Mental Status Schedule; Osteocalcin; Parathyroid Hormone; Peptide Fragments; Peptides; Procollagen; Prospective Studies; Risk Factors; Vitamin D

calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss, with an enhanced risk of osteoporotic fractures. Although hip fractures are a serious consequence, few therapeutic measures are given for primary or secondary prevention. A combination of calcium and vitamin D may not be the most effective treatment for all patients.. to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis, bone mineral density and fracture type, and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients.. a population-based, prospective cohort study.. 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture. This ward accepts people who live at home and are independent in activities of daily living. All subjects had a baseline medical examination, biochemical tests (parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) and were referred for bone densitometry.. at 68%, the prevalence of hypovitaminosis D (25-hydroxyvitamin D<30 nmol/l) was high. However, only half the patients had evidence of secondary hyperparathyroidism, the rest having a low to normal level of parathyroid hormone ('functional hypoparathyroidism'). Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium, higher 1,25-dihydroxyvitamin D, lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the 'functional hypoparathyroid' group (P<0.01).. there is a high prevalence of hypovitaminosis D in active, elderly people living at home who present with a hip fracture. However, secondary hyperparathyroidism occurs in only half of these patients. This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover, leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures. Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients, but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and 'vitamin D-replete' subjects needs further evaluation.

Topics: Aged; Aged, 80 and over; Bone Density; Calcium; Femur Neck; Hip Fractures; Humans; Hypoparathyroidism; Lumbar Vertebrae; Parathyroid Hormone; Prevalence; Prospective Studies; United Kingdom; Vitamin D; Vitamin D Deficiency

The purpose of this prospective study was to monitor the bone mineral density (BMD) of the lumbar spine and contralateral femoral neck in the first year following an osteoporosis-related fracture of the hip. Eighty-three elderly patients (mean age 77 years) who had sustained a hip fracture had determinations of BMD made at the time of fracture; 49 of these patients were available for reassessment of BMD 1 year later. The change in BMD was correlated with pre- and postinjury variables, such as ambulatory ability, dietary intake of calcium, serum vitamin D levels, mental status, and routine serologies. The mean decrease in BMD in the year following fracture was 5.4% from the contralateral femoral neck and 2.4% from the lumbar spine. Calcium intake correlated with the loss of BMD from the femoral neck (p = 0.015), but not the lumbar spine. Patients with daily calcium intakes of less than 500 mg/day had a more than 10% decrease in femoral neck BMD in the year following their hip fracture. Serum 1,25-dihydroxy vitamin D level correlated with loss of MBD from the lumbar spine (p = 0.001), but not from the femoral neck. There was no correlation between the loss of bone mineral from either measurement site and age, sex, level of ambulation, or mental status. The loss of BMD from the femoral neck in the year following a hip fracture is more than five times that reported in the nonfractured population. This accelerated rate of loss can have drastic consequences in an elderly population already exhibiting osteopenia and propensity to fall. Investigation of pharmacologic or other interventions in the first critical year following a hip fracture may potentially blunt this accelerated rate of bone loss and lessen the risk of subsequent fractures.

Topics: Aged; Aged, 80 and over; Biomarkers; Bone Density; Calcium, Dietary; Female; Femur Neck; Follow-Up Studies; Hip Fractures; Humans; Longitudinal Studies; Lumbar Vertebrae; Male; Mental Health; Middle Aged; Nutritional Status; Osteoporosis; Prospective Studies; Vitamin D