Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study.

In this post hoc analysis of the VITdAL-ICU study, an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml, vitamin D3 did not have a significant effect on ß-Crosslaps and osteocalcin. INTRODUCTION: Observational studies have shown accelerated bone loss in ICU survivors. A reversible contributor is vitamin D deficiency. In a post hoc analysis of the VITdAL-ICU study, we evaluated the effect of high-dose vitamin D3 on the bone turnover markers (BTM) ß-Crosslaps (CTX) and osteocalcin (OC). METHODS: The VITdAL-ICU study was a randomized, double-blind, placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 (a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU). In this analysis on 289 survivors (209 telephone, 80 personal follow-up visits), BTM were analyzed on days 0, 3, 7, 28, and 180; self-reported falls and fractures were assessed. Bone mineral density (BMD) was measured after 6 months. RESULTS: At baseline, CTX was elevated; OC was low in both groups-after 6 months, both had returned to normal. There were no differences between groups concerning BTM, BMD, falls, or fractures. In linear mixed effects models, CTX and OC showed a significant change over time (p < 0.001, respectively), but there was no difference between the vitamin D and placebo group (p = 0.688 and p = 0.972, respectively). CONCLUSIONS: Vitamin D supplementation did not have a significant effect on BTM. Further studies should assess the effectiveness of vitamin D on musculoskeletal outcomes in ICU survivors.

Age-related prevalence of osteoporosis and fragility fractures: real-world data from an Austrian Menopause and Osteoporosis Clinic.

OBJECTIVES: Age and bone mineral density (BMD) are the most relevant determinants for public health authorities to govern the management of osteoporosis. The objectives of this study were to determine the age-related prevalence of osteopenia and osteoporosis according to WHO criteria and fragility fractures in middle-aged and older women. METHODS: Women ≥40 years, who were referred to a menopause and osteoporosis outpatient clinic for BMD measurements, were assessed for patient characteristics, BMD and previous fragility fractures of the hip, the distal forearm and the vertebrae. Only records of their initial consultations were used for data analysis. RESULTS: Between 1990 and 2012, 99,399 women, mean age 56.1 years, were referred to the clinic for BMD testing. Of the total population, 52.5% showed normal, 34.0% osteopenic and 13.5% osteoporotic BMD. Fragility fractures were reported by 6540 patients, with 3070 (47%) non-vertebral fractures, namely 2518 (38.5%) distal forearm and 552 (8.4%) hip fractures; 66.8% of patients with the non-vertebral fractures were <65 years. CONCLUSION: The prevalence of osteoporosis and fragility fractures in middle-aged women, < 65 years, is hitherto under-recognized. Measuring BMD alone is not sufficient to identify patients at risk for fractures. Supplemental screening for clinical risk factors already during perimenopause may be advantageous.

The role of calcium supplementation in healthy musculoskeletal ageing : An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF).

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

How long should women with postmenopausal osteoporosis be treated with a bisphosphonate?

Bisphosphonates are very frequently prescribed to women suffering from postmenopausal osteoporosis with or without fragility fractures. The present review was aimed to update the available information on the most efficient treatment duration. Studies on bisphosphonate treatment duration were identified by Medline up to January 2013. Bisphosphonates are very effective in the short as well as in the medium-term. However, the optimal duration of use has not been determined yet. Therefore, this review summarizes the long-term effects of bisphosphonates on surrogate parameters of fracture prevention, bone mineral density measurements, and bone turnover markers. An initial treatment period of 3-5 years is recommended. Then, the patient has to be re-evaluated for fracture risk, which depends on fracture status as well as on other health issues. Beyond that, life style factors such as regular physical activity as well as a sufficient intake of calcium and vitamin D or, if necessary supplementation of calcium and/or vitamin D play an essential part in fracture prevention.

Pregnancy- and lactation-associated transient osteoporosis of both hips in a 32 year old patient with osteogenesis imperfecta.

Combination of osteogenesis imperfecta (OI), pregnancy, and transient osteoporosis (TO) of the hip is rare, only a few cases have been published so far. We report a 32 year old woman with OI, with TO on the right hip in her late third trimester. Non-pharmacological measures such as non-weight-bearing resulted in complete remission. Shortly after weaning, TO of the contralateral hip developed and non-pharmacological measures remained ineffective this time. Under treatment with a prostaglandin I(2) analog (iloprost), i.v. bisphosphonate (pamidronate), calcium and vitamin D supplementation rapid improvement of pain and complete remission was achieved.

The effect of PTH(1-84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial.

UNLABELLED: We explored the effects of PTH(1-84) compared with strontium ranelate on bone remodeling as measured by bone remodeling markers in postmenopausal women with osteoporosis. Biochemical markers of bone formation were significantly increased after treatment with PTH(1-84) but not strontium ranelate, indicating a different mechanism of action between these agents. INTRODUCTION: PTH(1-84) and strontium ranelate (SR) are both known to reduce fracture risk in osteoporosis. Measuring changes in biochemical markers of bone turnover induced by these agents can help in characterizing the action of PTH(1-84) and SR on bone remodeling. METHODS: A 24-week, randomized, open-label, parallel group, phase IV trial was conducted in 81 postmenopausal women with primary osteoporosis (≥50 years of age, lumbar spine, or total hip T-score ≤-2.5 SD) to assess the effect of SR as compared to PTH(1-84) on bone formation markers P1NP and BSAP. The bone resorption marker CTX was also measured. Subjects were randomly assigned to receive daily either 100 µg PTH(1-84) (n = 41) (subcutaneous injection) or oral 2 g SR (n = 40) for 24 weeks with daily supplements of 800 IU vitamin D(3) and 1,000 mg calcium. Patient-reported outcomes were collected to investigate the effect of treatment on quality of life (QoL). RESULTS: Percentage changes from baseline in P1NP and BSAP were significantly increased for PTH(1-84) by week 24 compared with SR (p < 0.0001). Significant changes from baseline in P1NP and BSAP were noted for PTH(1-84) from week 4 onwards; no significant changes were noted for SR. A trend towards a positive impact on QoL was seen with PTH(1-84) treatment. Safety profiles concur with previous analyses. CONCLUSIONS: PTH(1-84) had a more rapid and higher effect on bone formation markers compared to SR, indicating that SR has a different mode of action on bone remodeling than the bone building agent PTH(1-84) in postmenopausal women with osteoporosis.

Interaction between psychotropic drugs and thyroid hormone metabolism--an overview.

Psychotropic drugs can influence synthesis and metabolism of thyroid hormones at different sites. Generally, lithium, tricyclic antidepressants and phenothiazines lead to a reduction in synthesis and/or metabolism of thyroid hormones. The induction of autoimmune thyroid disorders by lithium and phenothiazines has been proven in animal studies and possibly can also be found in humans. Antipsychotic drugs generally exert their therapeutic effects through a modulation of the monoaminergic and serotoninergic system. At the hypothalamic level, thyrotropin releasing hormone (TRH) is controlled by the monoamonergic system and by serotonin. Depending on the specific species, there is a particular and different influence on the secretion of different hypothalamic-pituitary-thyroid (HPT)-axis hormones.

Daily oral magnesium supplementation suppresses bone turnover in young adult males.

This study examined the effects of daily oral magnesium (Mg) supplementation on bone turnover in 12 young (27-36 yr old) healthy men. Twelve healthy men of matching age, height, and weight were recruited as the control group. The study group received orally 15 mmol Mg (Magnosolv powder, Asta Medica) daily in the early afternoon with 2-h fasting before and after Mg intake. Fasting blood and second void urine samples were collected in the early morning on days 0, 1, 5, 10, 20, and 30, respectively. Total and ionized Mg2+ and calcium (Ca2+), and intact PTH (iPTH) levels were determined in blood samples. Serum biochemical markers of bone formation (i.e. C-terminus of type I procollagen peptide and osteocalcin) and resorption (i.e. type I collagen telopeptide) and urinary Mg level adjusted for creatinine were measured. In these young males, 30 consecutive days of oral Mg supplementation had no significant effect on total circulating Mg level, but caused a significant reduction in the serum ionized Mg+ level after 5 days of intake. The Mg supplementation also significantly reduced the serum iPTH level, which did not appear to be related to changes in serum Ca2+ because the Mg intake had no significant effect on serum levels of either total or ionized Ca2+. There was a strong positive correlation between serum iPTH and ionized Mg2+ (r = 0.699; P < 0.001), supporting the contention that decreased serum iPTH may be associated with the reduction in serum ionized Mg2+. Mg supplementation also reduced levels of both serum bone formation and resorption biochemical markers after 1-5 days, consistent with the premise that Mg supplementation may have a suppressive effect on bone turnover rate. Covariance analyses revealed that serum bone formation markers correlated negatively with ionized Mg2+ (r = -0.274 for type I procollagen peptide and -0.315 for osteocalcin), but not with iPTH or ionized Ca2+. Thus, the suppressive effect on bone formation may be mediated by the reduction in serum ionized Mg2+ level (and not iPTH or ionized Ca2+). In summary, this study has demonstrated for the first time that oral Mg supplementation in normal young adults caused reductions in serum levels of iPTH, ionized Mg2+, and biochemical markers of bone turnover. In conclusion, oral Mg supplementation may suppress bone turnover in young adults. Because increased bone turnover has been implicated as a significant etiological factor for bone loss, these findings raise the interesting possibility that oral Mg supplementation may have beneficial effects in reducing bone loss associated with high bone turnover, such as age-related osteoporosis.

Skeletal response to dietary zinc in adult female mice.

The current studies were intended to assess dose- and time-dependent effects of dietary zinc (Zn) on alkaline phosphatase (ALP) activity and tartrate-resistant acid phosphatase (TRAP) activity in adult female mice. In the first study, mice were given 0, 1x, 2x, 3x, or 4x normal dietary Zn for 2 weeks, 4 weeks, or 6 weeks. In the second study, mice were given 0, 1x, 2x, 3x, 4x, and 5x normal dietary Zn for 4 weeks. Sera were collected for measurements of ALP and (in the second study) osteocalcin. Tibiae and calvaria were extracted for measurements of ALP, protein, and TRAP. The first study showed positive correlations between dietary Zn and serum ALP (4 and 6 weeks, P < 0.001), Zn and tibial ALP (2, 4, and 6 weeks, P < 0.03), and Zn and tibial protein (2, 4, and 6 weeks, P < 0.001), as well as a negative correlation between dietary Zn and tibial TRAP (2, 4, and 6 weeks, P < 0.001). Covariant analyses showed that serum ALP, tibial ALP, tibial protein, and tibial TRAP were affected by the dose of Zn (P < 0.005) and by the treatment time (P < 0.03). Supplemental studies showed that (1) the dose-dependent effect of dietary Zn on serum ALP (at 6 weeks) was proportional to the effects on tibial ALP and calvarial ALP, but not to the effects of Zn on renal, hepatic, or intestinal ALP; (2) 6 weeks of dietary Zn caused dose-dependent increases in ALP specific activity in the tibia, calvaria, and liver, but not kidneys or intestines; and (3) Zn increased ALP activity and cell layer protein and decreased TRAP activity in monolayer cultures of the murine osteoblastic cell line, MC3T3-E1. The second dietary study confirmed the results of the first: 4 weeks of treatment with Zn caused significant increases in serum ALP, calvarial ALP, and tibial ALP activities, and a significant decrease in tibial TRAP (P < 0.05-0.005 for each). This study also revealed an effect of Zn to increase serum osteocalcin (P < 0.03 at 2x normal Zn). Together, these data indicate that incremental increases in dietary Zn are associated with increases in ALP activity in serum and in bone. The effect of Zn to decrease TRAP activity in osteoblast-line cells precludes the interpretation of a Zn-dependent decrease in tibial TRAP activity as evidence of decreased bone resorption.