Hypovitaminosis D in patients with osteoporotic hip fractures

BackgroundInadequate serum vitamin D levels are associated with secondary hyperparathyroidism, increased bone turnover, bone loss and increased fracture risk. Vitamin D is well recognized to be suboptimal in older patients when compared to age-matched controls. There are no published studies on the prevalence of hypovitaminosis D in Indian population with fragility fractures around the hip associated with osteoporosis and comminution at the fracture site.AimTo investigate the prevalence of hypovitaminosis D in patients admitted with osteoporotic hip fractures and associated fracture site comminution in a South Indian Institute.Material & MethodsA prospective cross sectional study was conducted on 100 patients admitted with osteoporotic hip fracture. Measurement of serum 25-hydroxy vitamin D was done and the same was correlated with the degree of osteoporosis using Singh’s index and fracture site comminution.ResultsOut of 100 patients studied, 92% had hypovitaminosis D with mean vitamin D level of 16.08 ± 5.95 ng/dl (65% vitamin D deficiency with mean 13.16 ± 4.24 ng/dl and 27% vitamin D insufficiency with mean 23.11 ± 2.62 ng/dl) and 94% had osteoporosis with Singh’s index grade 3 or less. Out of the 36 patients with fracture site comminution 34 patients (94%) had hypovitaminosis D and 33 patients (91.6%) had osteoporosis. Statistical significance was established for all the variables.ConclusionSignificant association was found between hypovitaminosis D, osteoporosis and fracture site comminution. High prevalence of hypovitaminosis D in patients presenting with hip fractures and fracture site comminution implicates the necessity for proper evaluation and effective supplementation of vitamin D in elderly patients along with anti-osteoporotic regimens for effective prevention and appropriate management of osteoporotic hip fractures.     

Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study

INTRODUCTION: Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3) have yielded conflicting results. The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D (25-OH D), bone turnover markers, bone mineral density (BMD), radius bone loss and incidence of fracture in postmenopausal women. METHODS: 669 postmenopausal women (mean age: 62.2 years) belonging to a population-based cohort were followed prospectively for a median of 11.2 years. At baseline, 25-OH D levels, BMD, bone turnover markers and clinical risk factors of osteoporosis were assessed. BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs. RESULTS: 73% and 35% of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention. 11% of women had levels below 30 nmol/l. Serum 25-OH D correlated modestly with intact PTH (r(2)=0.023, p<0.0001), but not with bone turnover markers or BMD at the hip and radius after adjustment for age. When levels of 25-OH D were considered as a continuous variable, there was no significant association between 25-OH D levels and radius BMD loss or fracture risk. After adjustment for age, there was no significant difference in incidence of fracture, BMD, radius BMD loss, bone turnover markers, grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75, 50 or 30 nmol/l. CONCLUSIONS: In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency, vitamin D status may not be an important determinant of bone health.     

Is there a differential response to alfacalcidol and vitamin D in the treatment of osteoporosis?

There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)₂D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)₂D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 μg twice daily improved calcium absorption, decreased serum PTH, and reduced alkaline phosphatase, whereas vitamin D₂ 500–1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of elderly women with vertebral osteoporosis.     

The effect of a short course of calcium and vitamin d on bone turnover in older women

Calcium and vitamin D (1200 mg/day + 800 IU) has been shown to reduce hip fracture incidence in older women living in long-term care facilities who had borderline low vitamin D levels. We examined the effect of a short course of calcium and vitamin D on biochemical markers of bone turnover in older community-living women. Twelve community-living women (mean age 75 years) in good general health, without diseases or on medications known to affect bone, were entered into the study. All women were treated with calcium citrate (1500 mg/day of elemental calcium) and vitamin D₃ (1000 IU/day) (Ca + D) for 6 weeks. Biochemical markers of bone turnover were measured in serum and urine collected at baseline (two samples), 5 and 6 weeks on Ca + D, and 5 and 6 weeks after termination of Ca + D. Markers of bone formation were osteocalcin, bone alkaline phosphatase and type I procollagen peptide. Markers of bone resorption were urinary hydroxyproline, free pyridinoline and deoxypyridinoline crosslinks, and N-telopeptides of type I collagen. Parathyroid hormone (PTH) and 25-hydroxyvitamin D were also measured at baseline, 6 weeks on treatment and 6 weeks after termination of treatment. All markers of bone resorption decreased on Ca + D and returned to baseline after termination of Ca + D (p<0.05). Markers of bone formation did not change with Ca + D treatment. PTH decreased on Ca + D and returned to baseline after treatment, and 25-hydroxyvitamin D increased with treatment and remained elevated 6 weeks after the end of treatment. We conclude that Ca + D reduces bone resorption in older women, possibly by suppressing PTH levels.     

Calcaneal Ultrasound but Not Bone Turnover Predicts Fractures in Vitamin D Deficient Frail Elderly at High Risk of Falls

Background Biochemical markers of bone turnover have been reported to predict fracture risk independent of bone mass in postmenopausal women. We investigated their use in predicting fractures in the frail elderly. Methods Cases were 151 low trauma fractures. For each case, a control was selected marched for sex, age, institution type and follow-up period. We measured two bone resorption markers (serum ICTP and serum CTX-I) and two bone formation markers (serum PINP and serum BAP). Quantitative Ultrasound (QUS) was measured in the calcaneus. Fractures were ascertained by x-ray reports. Results The mean age of subjects was 86.8 years (± 5.8 SD) and 86% were female. 76% had hypovitaminosis D (a serum 25 hydroxy vitamin D (25OHD) level < 39 nmol/L) and 81% had BUA < 67.4 dB/MHz (corresponding to a BMD T-score < −2.5). No significant differences in bone turnover markers were detected between fracture cases and their matched controls. In contrast, there was a significant difference between cases and controls for both broadband ultrasound attenuation (BUA) and velocity of sound (VOS) (both P < 0.05). These results remained the same after adjusting for weight, lower leg length and walking aids as well as the higher falls incidence in cases than controls (average 2.7 vs 0.9 falls respectively; P < 0.001) during the follow-up period. Conclusion In the frail elderly with vitamin D deficiency and high falls risk, calcaneal ultrasound but not markers of bone turnover were associated with fractures.     

Strategy for prevention of hip fractures in patients with Parkinson’s disease

Hypovitaminosis D and K due to malnutrition or sunlight deprivation,increased bone resorption due to immobilization,low bone mineral density(BMD)and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Parkinson’s disease.The purpose of the present study was to clarify the efficacy of interventions intended to prevent hip fractures in elderly patients with Parkinson’s disease.Pub Med was used to search the literature for randomized controlled trials(RCTs)regarding Parkinson’s disease and hip fractures.The inclusion criteria were 50 or more subjects per group and a study period of 1 year or longer.Five RCTs were identified and the relative risk and95%confidence interval were calculated for individual RCTs.Sunlight exposure increased serum hydroxyvitamin D[25(OH)D]concentration,improved motor function,decreased bone resorption and increased BMD.Alendronate or risedronate with vitamin D supplementation increased serum 25(OH)D concentration,strongly decreased bone resorption and increased BMD.Menatetrenone(vitamin K2)decreased serum undercarboxylated osteocalcin concentration,decreased bone resorption and increased BMD.Sunlight exposure(men and women),menatetrenone(women),alendronate and risedronate with vitamin D supplementation(women)significantly reduced the incidence of hip fractures.The respective RRs(95%confidence intervals)according to the intention-to-treat analysis were 0.27(0.08,0.96),0.13(0.02,0.97),0.29(0.10,0.85)and 0.20(0.06,0.68).Interventions,including sunlight exposure,menatetrenone and oral bisphosphonates with vitamin D supplementation,have a protective effect against hip fractures elderly patients with Parkinson’s disease.     

Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study.

The mechanisms leading to increased bone loss and skeletal fragility in women with postmenopausal osteoporosis are still poorly understood. Increased bone resorption, low serum estradiol and high serum sex-hormone-binding globulin (SHBG) recently have been reported as predictors of vertebral and hip fractures in elderly women. In a cohort of healthy untreated younger postmenopausal women aged 50-89 years (mean, 64 years), we compared baseline levels of bone markers and endogenous hormones in 55 women who subsequently had a fracture (20 vertebral and 35 peripheral fractures) with levels in the 380 women who did not fracture during a mean 5 years of follow-up. Women with levels in the highest quartile of four bone resorption markers including urinary-free deoxypyridinoline (D-Pyr), urinary type I collagen N-telopeptides (NTX), and urinary and serum type I collagen C-telopeptides (CTX) had about a 2-fold increased risk of fractures compared with women with levels in the three lowest quartiles with relative risk (RR) and 95% CI of 1.8 (1.0-3.4) for free D-Pyr, 1.7 (0.9-3.2) for urinary NTX, 2.3 (1.3-4.1) for urinary CTX, and 2.1 (1.2-3.8) for serum CTX. Serum levels of bone alkaline phosphatase (BAP) in the highest quartile were associated with an RR of fracture of 2.4 (1.3-4.2). Women with serum levels of estradiol and dehydroepiandrosterone (DHEA) sulfate in the lowest quartile had an RR of fracture of 2.2 (1.2-4.0) and 2.1 (1.2-3.8), respectively. Increased levels of SHBG and intact parathyroid hormone (PTH) were moderately associated with an increased risk of fracture. Similar results were obtained when the analysis was restricted to symptomatic vertebral and nonvertebral fractures. Adjustment of biochemical markers by hormone levels did not significantly alter the results. Women with both high bone resorption markers and low estradiol (or low DHEA sulfate) had a higher risk of fracture with RRs of 3.0-3.3 (p < 0.001). After adjustment for bone mineral density (BMD) of the hip, spine, radius, or total body, bone markers and hormones were still predictive of fracture risk with similar RRs. We conclude that high levels of some biochemical markers of bone turnover, low serum estradiol, low DHEA sulfate, high SHBG, and high PTH are associated with increased risk of osteoporotic fracture in postmenopausal women, independently of each other and of BMD. The mechanism by which some postmenopausal women have an increased rate of bone turnover leading to an increased risk of fracture remains to be elucidated.     

Vitamin D Deficiency and Its Influence on Bone Metabolism and Density in a Brazilian Population of Healthy Men

Vitamin D supplementation is universal for postmenopausal women, but not for elderly men, in whom osteoporosis is also commonly neglected. This study aimed to evaluate vitamin D deficiency and its association with secondary hyperparathyroidism, bone resorption, and bone density in Brazilian men. A total of 120 men, 20–93 years, were evaluated for serum calcium, phosphorus, creatinine, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, biochemical markers of bone resorption (carboxy-terminal telopeptide, carboxy-terminal peptide of type I collagen), and bone mineral density (dual-energy X-ray absorptiometry). Glomerular filtration rate (GFR) below 30?mL/min/1.73?m², chronic diseases, and medications affecting bone were the exclusion criteria. No participant reported previous low-impact fractures. In the overall population, 25(OH)D levels were below 30?ng/mL in 46.7%, and below 20?ng/mL in 27.6%. Among the 93 patients 50 years and older, 28 had osteoporosis. In those 70 years and older, the prevalence of vitamin D deficiency (42.1%), secondary hyperparathyroidism (46.4%), high bone resorption (39.6%), decreased GFR (39.2%), and osteoporosis (41.4%) was significantly higher than in the younger subjects (p?<?0.005 for all comparisons). Serum parathyroid hormone increased with aging and declining GFR, but was not significantly associated with 25(OH)D or bone mineral density. There was a clear contribution of vitamin D deficiency to increased bone resorption and osteoporosis. Binary logistic regression model considering age, 25(OH)D, and bone resorption identified age ≥70 years as the main determinant of osteoporosis. Our data demonstrate a high prevalence of vitamin D deficiency in a male population living in Rio de Janeiro, and emphasize its participation on the pathogenesis of age-related bone loss. (Vitamin D deficiency and osteoporosis are common in elderly Brazilian men.)     

Acute Effects of Calcitonin Nasal Spray on Serum C-telopeptide of Type 1 Collagen (CTx) Levels in Elderly Osteopenic Women with Increased Bone Turnover

Salmon calcitonin is a potent inhibitor of osteoclastic activity. The effect of calcitonin in elderly women with high bone turnover at higher risk of developing osteoporosis has not been studied. To investigate acute effects of calcitonin treatment on bone resorption markers in elderly women, we conducted a randomized trial in women >65 years of age with high bone turnover assessed as urinary N-telopeptide of type-I collagen (NTx) levels 1 SD higher than mean premenopausal levels, which was irrespective of bone density. A total of 98 elderly women were randomly assigned to receive either 200 IU calcitonin nasal spray (n = 75) with calcium (500 mg) and vitamin D (200 IU) or calcium and vitamin D (n = 23) alone for 6 months. Blood and urine samples were collected at 0, 2, 4, and 6 months and analyzed for urinary NTx and serum C-telopeptide of type-1 collagen (CTx). At baseline, mean age was 72.1 ± 4.7 (mean ± SD) in the calcitonin group and 72.2 ± 6 years in the control group. The spine and total hip BMD, serum PTH levels and urinary calcium/creatinine ratios were similar in both groups. Mean BMD was in the osteopenic range in both groups. Calcitonin treatment resulted in significant decreases in serum CTx levels, 2, 4 and 6 months after treatment as compared to baseline, and after 4 and 6 months as compared to controls. A maximum decrease from baseline of 33% was seen at 6 months. The urinary resorption marker, urine NTx, showed a significant decrease in the calcitonin group when compared to baseline only at the 6-month time point. Analysis of least significance change (LSC) showed that 70% of calcitonin patients were categorized as responders using serum CTx after 6 months of treatment. We conclude that 200 IU calcitonin effectively decreases bone resorption within 60 days of therapy, thus preventing further bone loss in elderly women who are at a high risk of developing osteoporosis.     

Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures: the Geelong Osteoporosis Study.

In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures. INTRODUCTION: In a population of women who reside in a temperate climate and do not generally receive dietary vitamin D supplementation, we investigated whether seasonal vitamin D insufficiency is associated with increased risk of fracture. MATERIALS AND METHODS: An observational, cross-sectional, population-based study set in southeastern Australia (latitude 38-39 degrees S). Participants were drawn from a well-defined community of 27,203 women >/=55 years old: 287 randomly selected from electoral rolls, 1635 with incident fractures, and 1358 presenting to a university hospital with falls. The main outcome measures were annual periodicities of ultraviolet radiation, serum 25-hydroxyvitamin D [25(OH)D], serum parathyroid hormone (PTH), serum C-telopeptide (CTx), BMD, falls, and fractures. RESULTS: Cyclic variations in serum 25(OH)D lagged 1 month behind ultraviolet radiation, peaking in summer and dipping in winter (p < 0.001). Periodicity of serum PTH was the inverse of serum 25(OH)D, with a phase shift delay of 1 month (p = 0.004). Peak serum CTx lagged peak serum PTH by 1-2 months. In late winter, a greater proportion of falls resulted in fracture (p < 0.001). Seasonal periodicity in 439 hip and 307 wrist fractures also followed a simple harmonic model (p = 0.078 and 0.002, respectively), peaking 1.5-3 months after the trough in 25(OH)D. CONCLUSIONS: A fall in 25(OH)D in winter is accompanied by increases in (1) PTH levels, (2) bone resorption, (3) the proportion of falls resulting in fracture, and (4) the frequency of hip and wrist fracture. Whether vitamin D supplementation in winter can reduce the population burden of fractures requires further investigation.     

Effect of age-related chronic immobility on markers of bone turnover.

The effects of acute immobilization on bone turnover are well known, but the effects of chronic hypomobility with aging have not been studied. In a cohort of 1064 frail elderly subjects, immobility was significantly associated with serum PINP but not serum CTx after adjusting for confounders. The effect of immobility may be more marked on bone formation than on bone resorption. INTRODUCTION: Accelerated bone turnover and rapid bone loss caused by acute immobilization is well recognized, but the effects of age-related chronic reduction in mobility on bone turnover have been less well studied. We assessed the associations between bone turnover and measures of mobility in a cohort of elderly subjects. MATERIALS AND METHODS: We measured serum levels of the aminoterminal propeptide of type I collagen (PINP), a marker of bone formation, and serum concentrations of the carboxyterminal telopeptide of type I collagen (CTx), a marker of bone resorption, as well as serum intact PTH, serum 25 hydroxyvitamin D (25OHD), mobility, and static balance in a well-characterized sample of 1064 elderly men and women living in residential aged care facilities. Serum creatinine, phosphate, albumin, and calcium were measured in a randomly selected subgroup of 447 subjects. RESULTS: The subjects were elderly and frail; their mean age was 86.0 years (range, 65-101 years); 69% used a walking aid; and 77% were vitamin D deficient (serum 25OHD level < 39 nM). Both serum PINP and CTx increased with age in both sexes. Elevated PINP or CTx was significantly correlated with high PTH, creatinine, and albumin in both genders, except for albumin in women. Age- and gender-adjusted serum CTx and PINP were significantly higher in those with poorer mobility and those with worse static balance. In multivariate analyses, higher serum PINP but not CTx was associated with poorer mobility and worse static balance. CONCLUSIONS: Our findings suggest that poor mobility contributes to the state of accelerated bone turnover usually seen in the elderly. The effect of chronic relative immobility may be more marked on bone formation than bone resorption.     

Severe vitamin D deficiency in Swiss hip fracture patients

BACKGROUND: Most clinical guidelines for the prevention of hip fractures recommend 800 IU vitamin D per day. This dose shifted serum 25-hydroxyvitamin D levels (25(OH)D) in previous studies to between 60 and 100 nmol/l. AIM: To measure 25(OH)D levels and prevalence of vitamin D supplementation in individuals age 65+ with acute hip fracture. METHODS: 222 consecutive hip fracture patients were investigated over a 12 month period. Mean age of patients was 86 years and 77% were women. RESULTS: Mean serum 25(OH)D levels were low among hip fracture patients admitted from home (34.6 nmol/l), from assisted living (27.7 nmol/l), and from nursing homes (24 nmol/l). Severe vitamin D deficiency below 30 nmol/l was present in 60%, 80% were below 50 nmol/l, and less than 4% reached desirable levels of at least 75 nmol/l. Consistently, only 10% of hip fracture patients had any vitamin D supplementation on admission to acute care with significantly higher 25(OH)D levels among individuals supplemented with 800-880 IU/day (63.5 nmol/l). Controlling for age and gender, vitamin D supplementation, type of dwelling, and season were independently and significantly associated with 25(OH)D levels. CONCLUSION: These data provide evidence that current guidelines for the prevention of hip fractures need further effort to be translated into clinical practice.     

Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis

Vertebral osteoporosis, a common disorder in elderly women, is characterized by a wide spectrum of bone turnover abnormalities on iliac crest biopsy. The level of bone formation can be assessed noninvasively by measuring serum osteocalcin, whereas conventional biochemical markers of bone resorption lack specificity and do not reflect bone resorption assessed from histology. We measured the urinary excretion of pyridinoline crosslinks Pyr and D-Pyr, a specific marker of bone and cartilage collagen degradation, along with serum osteocalcin and urinary hydroxyproline, in 36 elderly women with vertebral osteoporosis who had a simultaneous iliac crest biopsy. Urinary pyridinoline crosslinks, but not hydroxyproline, correlated significantly with histologic resorption, assessed by the osteoclast surface (r = 0.35, p less than 0.05 for Pyr; r = 0.46, p less than 0.01 for D-Pyr). In addition, Pyr and D-Pyr were correlated with the bone formation rate as well as serum osteocalcin, with correlation coefficients ranging from 0.69 to 0.80, p less than 0.0001. These data indicate that Pyr and D-Pyr are sensitive markers of bone turnover in elderly women with vertebral osteoporosis. The poor correlation between the level of urinary collagen crosslinks and histological assessment of bone resorption indicates the low sensitivity of iliac crest histomorphometry in the measurement of resorption rate of the skeleton.     

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency

Significant reduction in bone mineral density (BMD) occurs in patients with Parkinson's disease (PD), correlating with immobilization and with vitamin D deficiency, and increasing the risk of hip fracture, especially in elderly women. As a biological indicator of compromised vitamin K status, an increased serum concentration of undercarboxylated osteocalcin (Oc) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women. We evaluated treatment with vitamin K(2) (menatetrenone; MK-4) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD. In a random and prospective study of PD patients, 60 received 45 mg of MK-4 daily for 12 months, and the remaining 60 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K(1) deficiencies, high serum levels of ionized calcium, and glutaminic residue (Glu) Oc, and low levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D], indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion. BMD in the second metacarpals increased by 0.9% in the treated group and decreased by 4.3% in the untreated group (p < 0.0001). Vitamin K(2) level increased by 259.8% in the treated group. Correspondingly, significant decreases in Glu Oc and calcium were observed in the treated group, in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures (eight at the hip and two at other sites) in the untreated group, and one hip fracture occurred among treated patients (p = 0.0082; odds ratio = 11.5). The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration, and it can also decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1,25-(OH)(2)D concentration.     

Impairment of bone turnover in elderly women with hip fracture

Summary Hip fracture is one of the most severe consequences of osteoporosis affecting aged women. However, abnormalities of bone turnover responsible for bone loss in this condition have not been clearly defined. To further evaluate the bone metabolic status of women sustaining hip fracture, we have prospectively measured serum osteocalcin as a marker of bone formation and urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-pyr) cross-links as markers of bone collagen degradation in 174 independently living women (80 ± 8 years) within a few hours after a hip fracture. Comparison was made with 77 age-matched controls (80 ± 5 years) and 17 premenopausal women (39 ± 3 years). In addition 15 of the patients were followed with daily measurements during the first postoperative week. At the time of admission osteocalcin was 20% lower in the fractured women compared to the elderly controls (7.6 ± 3.8 vs. 9.5 ± 4.5 nglml,P = 0.001). Pyr and D-pyr were 36% and 40% higher, respectively (P = 0.0001), than in elderly controls and 85% and 76% higher than in premenopausal controls (P = 0.0001). Serum osteocalcin did not correlate with the cortisol level measured at the same time (r = 0.03, ns), nor with serum albumin and creatinine. Serum osteocalcin remained unchanged within 18 hours after fracture, whereafter it progressively decreased until the third postoperative day. No correlation was noted between the excretion of pyridinoline cross-links and the time elapsed from fracture.These data suggest that the abnormal levels of osteocalcin and pyridinolines are unrelated to traumatically induced acute changes, but reflect abnormalities of bone turnover existing prior to the fracture. Thus, hip-fracture patients have biochemical evidence of decreased bone formation and increased bone resorption when compared to age-matched controls. We suggest that these abnormalities may play a role in the decrease of the bone mass and the consequently increased bone fragility that characterize the osteoporotic hip fracture in the elderly.     

Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and may have osteoporosis. We previously showed deficiency of vitamins D and K1 causes reduced bone mineral density (BMD) in female AD patients. The present study was undertaken to address the possibility that treatment with vitamin K2 (menatetrenone; MK-4) may maintain BMD and reduce the incidence of nonvertebral fractures in elderly female patients with AD. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K1 deficiencies. They also had high serum levels of parathyroid hormone (PTH) and Glu osteocalcin (OC) and low serum ionized calcium, indicating that vitamin D deficiency stimulates compensatory PTH secretion. During the 2-year study period, BMD in the second metacarpals increased by 2.3% in the treated group and decreased by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 284.9% and 147.9%, respectively, in the treated group. Correspondingly, a significant decrease in Glu OC and PTH were observed, in association with an increased calcium levels, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Treatment with MK-4 and vitamin D2 with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures.     

Vitamin D levels in post-menopausal Korean women with a distal radius fracture

IntroductionThe purpose of this study was to investigate serum levels of vitamin D in post-menopausal Korean women with a distal radius fracture (DRF) and to determine if there is any association between vitamin D levels and bone-related variables such as bone mineral densities (BMDs), serum parathyroid hormone (PTH) levels and several bone turnover markers.Materials and methodsThe data of 104 postmenopausal women surgically treated for a distal radius fracture (DRF group) and 107 age-matched control patients without a fracture (control group) were compared. Serum vitamin D levels (25-hydroxycholecalciferol, 25(OH)D₃) were compared between the groups with consideration of age and seasonal variations. BMDs, serum PTH and several bone turnover markers, including serum osteocalcin, C-telopeptide and urine N-telopeptide, were measured and analysed to find any association with vitamin D levels.ResultsThe mean 25(OH)D₃ level was significantly lower in the DRF group compared to the control group (p < 0.001). In particular, patients in their sixth and seventh deciles in the DRF group had significantly lower 25(OH)D₃ levels than patients in the control group (p = 0.001 and 0.013, respectively). When seasonal variation was considered, significant differences of 25(OH)D₃ levels were found between the groups in autumn and winter. Hip BMDs were significantly lower in the DRF group than in the control group, and there was a positive correlation between serum 25(OH)D₃ levels and hip BMDs. Bone turnover markers were not significantly different between the two groups, although serum PTH levels were marginally higher in the DRF group (p = 0.08).ConclusionsPost-menopausal Korean women with a DRF were found to have significantly lower serum vitamin D levels than the control group, and vitamin D levels were particularly lower in women in their sixth and seventh deciles who may be a good target group for prevention of future fractures. Future investigation should focus on determining whether vitamin D supplementation can be helpful in preventing future fractures in patients with a DRF.     

Vitamin D and intact PTH status in patients with hip fracture

Introduction The prevalence of hypovitaminosis D in patients with acute hip fracture was examined in a population on Sado Island in Japan. There were 85 cases of hip fracture among this population in 2004, giving an overall incidence of hip fracture of 121.4 per 100,000 population per year. This study included 50 of the 85 cases, and these cases were defined as the hip fracture group. Patients older than 70 years without established osteoporosis who were admitted to the hospital on the island during almost the same period for treatment of an orthopedic condition other than a hip fracture were defined as the control group.Materials and methods The levels of serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (intact PTH), alkaline phosphatase (ALP), albumin, and the number of remaining teeth were examined in each group. In the hip fracture group, serum calcium, serum phosphorus, urine N-terminal cross-linking telopeptide of type I collagen (NTx), bone mineral density (BMD) of the nonfractured hip, the presence of a vertebral fracture on X-ray, severity of dementia, and physical activity level were also examined.Results Both the serum 25-OHD and serum albumin levels were significantly lower in patients with hip fracture than in controls, and the intact PTH level was significantly higher in patients with hip fracture. The number of remaining teeth was correlated with age, and was also significantly correlated with 25-OHD. In the hip fracture group, 62% of the subjects had hypovitaminosis D (25-OHD <20 ng/ml) and one-fifth of cases with hypovitaminosis D showed elevated PTH levels (>65 pg/ml). On the other hand, in the control group, hypovitaminosis D occurred in 18.9% of the subjects, and only one case showed elevated PTH. The serum 25-OHD level showed a decrease as the severity of dementia progressed and the activity level decreased.Conclusion Our results indicate that about two-thirds (62%) of hip fracture patients had vitamin D insufficiency, suggesting that this condition may be closely associated with hip fracture in elderly people. Therefore, the serum 25-OHD level may be a useful index for the risk of hip fracture in elderly people.     

Einfluss der Bisphosphonate auf die Frakturheilung

As the population ages and the prevalence of osteoporotic fractures increases, perioperative medical care of the elderly will continue to present challenges. Bisphosphonates, in combination with calcium and vitamin D have become the first-line therapy for patients with osteoporosis. Thus, one of the frequently asked questions concerning such patients is whether individuals who have recently sustained a fracture should take inhibitors of bone resorption. This discussion is relevant because many of the patients treated with bisphosphonates do have fractures, such as patients with osteoporosis, tumor bone disease, Paget's disease or osteogenesis imperfecta. A recent fracture should not preclude the initiation of therapy, because bisphosphonates have not been shown to interfere with overall fracture strength. Bisphosphonates appear to affect callus formation differently from either estrogen or raloxifene, but no significant difference in callus strength was seen 16 weeks after fracture. In addition, current studies demonstrate a significant reduction in periprosthetic bone loss after uncemented primary hip arthroplasty.