The influence of age on bone mineral regulating hormones

Epstein, Sol; Bryce, Graeme F.; Hinman, J.W.; Miller, O. Neal; Riggs, B. Lawrence; Hui, Siu L.; Johnston, C. Conrad

doi:10.1016/8756-3282(86)90001-3

Cited by 136 publications

(49 citation statements)

References 19 publications

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“…The low D-hormone serum levels observed with a creatinine clearance of <65 ml/min may also be one reason for the increased osteopenia and osteoporosis observed with low creatinine clearance by other authors [15,16]. Our result enhances the theory suggested by other studies [4,5,6,7,17,18,19,20,21,22] that D-hormone is an independent risk factor for falls [1,2,5,23], and that D-hormone is directly involved in the causal pathogenic pathway of decreased muscle strength related falls [9,23,24]. It has been recently confirmed in VDR gene deleted mice that the absence of VDR causes muscle abnormality independently of secondary metabolic changes, e.g.…”

Section: Discussionsupporting

confidence: 80%

Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65�ml/min

et al. 2004

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We previously observed that a creatinine clearance (CrCl) of <65 ml/min is a significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels. To test our hypothesis, we investigated in a post hoc analysis of a double-blind randomized study whether treatment with alfacalcidol, a synthetic prodrug of the D-hormone, can reduce the high incidence of fallers and the high risk of falls associated with low CrCl. Of 378 Swiss community-dwelling women (n=191) and men (n=187), aged 70 years and older, 191 received randomly 1 lg capsules of alfacalcidol (AlphaD3: Teva), and 187 received one capsule of placebo daily. With the help of questionnaires we regularly assessed the incidence and frequency of falls. The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65 ml/min. The presented results are from ITT analyses. In participants with a CrCl of <65 ml/min, the 36 weeks of treatment with alfacalcidol was, compared with placebo, associated with a significant reduction in the number of fallers (14/72 versus 25/70; OR 0.26, 95% CI 0.08-0.80, P=0.019), and a significant reduction of the number of falls (16/72 versus 28/70; OR 0.29, 95% CI 0.09-0.88, P=0.028). No such association was observed in participants with a CrCl of ‡65 ml/min (for fallers 26/120 versus 21/116; OR 0.92 95% CI 0.34-2.52, P=0.875; for falls 32/120 versus 23/116; OR 0.93 95% CI 0.34-2.54, P=0.885). In the placebo group frequency of falls was dependent on CrCl (P=0.006), whereas in the alfacalcidol treatment group frequency of falls was independent of CrCl (P=0.494). No cases of clinically relevant hypercalcemia were observed. In a community-dwelling population of elderly men and women with a CrCl of <65 ml/min, treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of falls.

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Section: Discussionsupporting

confidence: 80%

Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65�ml/min

et al. 2004

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“…Much evidence has shown that BMD decreases with increasing age in men, and is accompanied by decreasing sex hormones, but more moderately than in post-menopausal women [5,10,17,18,23,24]. According to previous studies, the high BMD or calcium content of the first and fourth lumbar vertebrae, femur, and tibia coincided with a high testosterone level at the age of 12 months in male Wistar rats [11,14,17].…”

Section: Discussionmentioning

confidence: 99%

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and Strength at Different Skeletal Sites in Male Rats.

Iida¹,

Fukuda²

2002

J. Vet. Med. Sci.

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ABSTRACT. Age-related changes in bone mineral density (BMD), cross-sectional area and strength strain index (SSI) of the long bones in the limbs and first lumbar vertebra of male Wistar rats were measured by a peripheral quantitative computed tomography (pQCT) method. One hundred and ten rats aged 2-30 months were used. The results indicate that the total (cortical + trabecular), cortical and trabecular BMD values of the metaphysis and cortical BMD values of the diaphysis in the long bones varied for each bone and differed from those of the first lumbar vertebra. The total BMD of long bones showed high values at 6-21 months and then decreased, but these did not always coincide with cortical and trabecular BMD. The values of SSI in the long bones varied. The values of total and cortical BMD and SSI of lumbar vertebra increased for 6-12 months and then decreased, but the trabecular BMD increased after 12 months. The total area in both the long bones and the first lumbar vertebra increased with the decrease in cortical area and the increase in the trabecular area with increasing age. It was concluded that age-related changes in bones, similar to those observed in humans, could be observed in some bones and parameters, although the age in rats when the so-called peak bone mass appears in the whole skeleton could not be clearly determined. KEY WORDS: age change, bone mineral density, male rat, peak bone mass, peripheral quantitative computed tomography (pQCT) J. Vet. Med. Sci. 64(1): 29-34, 2002 Rats are widely used for studies on bone metabolism and diseases such as osteoporosis, although their worth as an animal model has been contested [6,12,16,21] because their bone morphological patterns differ from those of humans. Rats show a modeling pattern from youth to old age, while humans show a modeling pattern in the growth stage which changes to a remodeling pattern after maturity [7]. The length and weight of long bones in rats continue to increase up to the old age due to the fact that both or either of the epiphysial growth plates do not close for a long time [8]. The cortical and trabecular bone components of the femur neck in rats have been found to be higher and lower, respectively, than those in humans [3].The age of peak bone mass, hereafter referred to as bone mineral density, in a human is considered a significant indicator for knowing the state of activity of bone metabolism and age of onset of osteoporosis, because thereafter the bone mass reduces with increasing age. To clarify whether rats show peak bone mass or not is an important matter for considering their worth as a model animal in bone researches and for determining corresponding ages between rats and humans in experimental procedures and assessing experimental results. That is, we are interested to know if rats have age-related changes in bone metabolism throughout their life similar to those in humans. We demonstrated that high values of mineral and organic contents at various skeletal sites are present in rats [11] and a peak of bone volume i...

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“…Renal function declines with advancing age and this is accompanied by a decrease in serum 1,25(OH) 2 D concentration (44) . As mentioned earlier, the effect of vitamin D supplementation on Ca absorption is attenuated by renal impairment (42) .…”

Section: Renal 1-a-hydroxylasementioning

confidence: 99%

Vitamin D and bone health outcomes in older age

2013

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The aim of this review is to summarise the evidence linking vitamin D to bone health outcomes in older adults. A plethora of scientific evidence globally suggests that large proportions of people have vitamin D deficiency and are not meeting recommended intakes. Older adults are at particular risk of the consequences of vitamin D deficiency owing to a combination of physiological and behavioural factors. Epidemiological studies show that low vitamin D status is associated with a variety of negative skeletal consequences in older adults including osteomalacia, reduced bone mineral density, impaired Ca absorption and secondary hyperparathyroidism. There seems to be inconsistent evidence for a protective role of vitamin D supplementation alone on bone mass. However, it is generally accepted that vitamin D (17 . 5 mg/ d) in combination with Ca (1200 mg/d) reduces bone loss among older white subjects. Evidence for a benefit of vitamin D supplementation alone on reducing fracture risk is varied. According to a recent Agency for Healthcare Research and Quality review in the USA the evidence base shows mixed results for a beneficial effect of vitamin D on decreasing overall fracture risk. Limitations such as poor compliance with treatment, incomplete assessment of vitamin D status and large drop-out rates however, have been highlighted within some studies. In conclusion, it is generally accepted that vitamin D in combination with Ca reduces the risk of non-vertebral fractures particularly those in institutional care. The lack of data on vitamin D and bone health outcomes in certain population groups such as diverse racial groups warrants attention. 25-hydroxyvitamin D: Vitamin D requirements: Older age: Bone mineral density: FracturesOsteoporosis is a condition characterised by a low bone mass and microarchitectural deterioration of bone with a consequent increase in bone fragility and susceptibility to fracture. In the UK, it is estimated that 3 million people are affected with osteoporosis. Furthermore, one in two British women and one in five British men aged > 50 years will experience an osteoporotic fracture in their lifetime with the estimated costs in the UK being about £1 . 7 billion annually. In the European Union, it has been estimated that previous and incident fractures accounted for 1 180 000 quality-adjusted life years lost during 2010 (1) . Furthermore, with an ageing population, the costs associated with treating osteoporosis in the EU are expected to increase by 25% in 2025(1) . Bone is a dynamic tissue that responds to the external and internal environments to which it is exposed during an individual's lifetime. While a considerable proportion (up to 70%) of the inter-individual variation in bone mass is genetically determined, lifestyle factors such as diet and exercise are well established modifiable factors of bone mass. Bone turnover is important for the self-repair of skeletal tissue (2) as well as maintaining mineral homoeostasis (e.g. Ca and P) and the balance between the rate of bone formation ...

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The influence of age on bone mineral regulating hormones

Cited by 136 publications

References 19 publications

Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65�ml/min

Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65�ml/min

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and Strength at Different Skeletal Sites in Male Rats.

Vitamin D and bone health outcomes in older age

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