Low Vitamin D Status, High Bone Turnover, and Bone Fractures in Centenarians

Passeri, Giovanni; Pini, Gian Andrea; Troiano, Leonarda; Vescovini, Rosanna; Sansoni, Paolo; Passeri, M; Gueresi, Paola; Delsignore, R; Pedrazzoni, M.; Franceschi, Claudio

doi:10.1210/jc.2003-030515

Cited by 119 publications

(68 citation statements)

References 54 publications

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“…In our study, the correlation between OPG and bone resorption was found in the old subjects who were under 85 years of age but not in the long-lived subjects. This finding was really unexpected, since several studies had already demonstrated that in the presence of osteoporosis, as found in long-lived subjects (25), serum OPG values should be strictly correlated with bone turnover (13 -16). Although we did not evaluate the bone structure in our subjects, the huge increase in serum bone resorption markers in long-lived subjects would suggest that the bone was impaired in this population, in agreement with previous observations (25).…”

Section: Discussionmentioning

confidence: 95%

“…This finding was really unexpected, since several studies had already demonstrated that in the presence of osteoporosis, as found in long-lived subjects (25), serum OPG values should be strictly correlated with bone turnover (13 -16). Although we did not evaluate the bone structure in our subjects, the huge increase in serum bone resorption markers in long-lived subjects would suggest that the bone was impaired in this population, in agreement with previous observations (25). Another interesting finding was the disappearance of a correlation between OPG and RANKL in long-lived subjects when the statistical analysis was performed by the multivariate instead of the univariate approach.…”

Section: Discussionmentioning

confidence: 95%

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Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism

Mazziotti¹,

Amato²,

Sorvillo³

et al. 2006

eur j endocrinol

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Aim: To evaluate serum osteoprotegerin (OPG) concentrations in relation to age-dependent changes in serum markers of bone metabolism and systemic inflammation. Methods: Two-hundred and eighty-three healthy subjects were evaluated for plasma estimated creatinine clearance (Cr-clearance), C-reactive protein (CRP), bone alkaline phosphatase, C-telopeptides of type-1 collagen (CrossLaps), nuclear factor-kappaB ligand (RANKL) and OPG concentrations. Results: In adult subjects (82 cases aged between 27 and 64 years) serum OPG concentrations were significantly and independently correlated with RANKL and Cr-clearance (R 2 : 0.29), but not with CRP and biochemical markers of bone metabolism. In old subjects who were between 65 and 84 years of age (52 cases) serum OPG concentrations were significantly higher as compared with the adult subjects and correlated independently and significantly with serum RANKL, Cr-clearance and CrossLaps values (R 2 : 0.63). The highest OPG values were found in the long-lived subjects (149 cases with ages between 85 and 110 years) who also showed increased serum CrossLaps and CRP concentrations as compared with the younger subjects. However, in the long-lived subjects serum OPG concentrations were significantly and independently correlated with Cr-clearance and CRP (R 2 : 0.45) but not with CrossLaps values. Conclusions: These data would suggest that different factors might be responsible for the age-dependent enhancement of OPG production. Bone metabolism would seem to be the most important factor influencing serum OPG concentrations in old subjects under 85 years of age, whereas in long-lived subjects the circulating values of this cytokine seem to be mainly correlated with serum CRP which could be a marker of inflammation and cardiovascular risk.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism

Mazziotti¹,

Amato²,

Sorvillo³

et al. 2006

eur j endocrinol

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“…In addition, correlations were found between PTH and calcium (r = −0.33, p < 0.001), IL-6 and S-CTX (r = 0.37, p < 0.001), IL-6 and calcium (r = −0.35, p < 0.001), PTH and IL-6 (r = 0.24, p = 0.019). There was no correlation between the creatinine clearance and PTH (r = −0.167, p = not significant) (Passeri et al, 2003).…”

Section: Bone Metabolism In Centenariansmentioning

confidence: 89%

“…There was also a significant correlation between markers of bone turnover and ultrasonographic parameters both at the phalanges and at the calcaneous: PTH and S-CTX versus phalangeal UBPI (r = −0.38, p = 0.032; r = −0.28, p = 0.036, respectively), S-CTX versus calcaneal SoS (r = −0.4, p = 0.05) (Passeri et al, 2003). …”

Section: Bone Metabolism In Centenariansmentioning

confidence: 91%

Calcium metabolism and vitamin D in the extreme longevity

Passeri

Vescovini

Sansoni

et al. 2008

Experimental Gerontology

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Skeletal remodelling is a continuous process during life and is still active also in extreme senescence. In the elderly, bone resorption often prevails over bone formation, causing bone loss and fragility. Elderly subjects are exposed to the risk of fractures, and loss of self-sufficiency, if considering that the proximal femur is the most frequently involved site. Bone remodelling can maintain circulating calcium within physiological ranges, at the expense of a substantial loss of this ion from the skeleton, particularly during senescence. Calcium metabolism is regulated at cellular/molecular level by a network of cytokines, growth factors, systemic hormones that act on bone in paracrine/autocrine/ systemic fashion. Among the molecules involved in bone metabolism, parathyroid hormone (PTH) and vitamin D present some peculiar aspects during senescence. The osteometabolic features in a consistent group of centenarians have been evaluated. It results that a severe hypovitaminosis D was present in 99 out of 104 centenarians (25-OH vitamin D below 5 nmol/L), and that it plays an important role as a factor inducing a vicious circle involving hypocalcemia, secondary hyperparathyroidism, together with biochemical features indicating a consistent bone loss. Serum C-terminal cross-linking telopeptide, a specific marker of bone resorption was elevated in 92% of these subjects. Moreover, it has been found that several femoral fractures had occurred after 90 years of age. These data offer a rational for the possible prevention of elevated bone turnover, bone loss and consequently the reduction of osteoporotic fractures and fractures-induced disability, in the oldest olds, through the simple supplementation with calcium and vitamin D.

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“…In addition, their skin exposure to the solar ultraviolet B spectrum is often limited owing to a sedentary lifestyle or complete institutionalization. In line with these considerations, more than 95% of a cohort of centenarians had undectable 25(OH)D levels [6]. Interestingly, an anecdotal report of one of the oldest men who ever lived, a Ukrainian who recently died at the age of almost 120 years, informs us that this man ate herring, one of the very few vitamin D-rich foods, several times a week.…”

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confidence: 93%

Can Vitamin D Deficiency Impact Cardiovascular Health in the Elderly?

Zittermann

2008

Aging Health

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we should not be too enthusiastic that simple vitamin D supplementation in middle-aged to elderly adults will solve all vitamin D-related problems.'Life expectancy is increasing worldwide. Nevertheless, the burden of cardiovascular disease (CVD) morbidity and mortality is still high in developed countries and is rapidly increasing in developing countries [1]. During the last decade, it also became clear that insufficient and even deficient vitamin D status is a worldwide problem [2]. By far the most important reason for this phenomenon is an inadequate skin exposure to solar ultraviolet B radiation, since ultraviolet B-induced skin synthesis is the major source of vitamin D for humans. It has long been known that vitamin D plays a major role in bone mineral homeostasis by promoting the transport of calcium and phosphate to ensure adequate blood levels of these ions for normal bone mineralization. Bone diseases such as rickets and osteomalacia are well-known consequences of vitamin D deficiency in infants and adults, respectively. However, is there any rationale to assume that vitamin D deficiency might be a causal factor of CVD-related morbidity and mortality?In the last several decades, many studies have documented nontraditional roles of vitamin D, including immunomodulatory properties and the regulation of intracellular calcium concentrations. There is now increasing evidence that 1,25-dihydroxyvitamin D exerts important physiological actions in the vasculature. These mechanisms include the inhibition of vascular smooth muscle proliferation, the suppression of vascular calcification, the downregulation of proinflammatory cytokines, the upregulation of anti-inflammatory cytokines and the action of vitamin D as a negative endocrine regulator of the renin-angiotensin system. Studies in knockout mice have confirmed that the absence of vitamin D-receptor activation leads to hypertension, left ventricular hypertrophy and disturbed blood coagulation.Ecological studies have reported higher rates of coronary heart diseases and hypertension with increasing distance from the equator, a phenomenon that could be attributed to the higher prevalence of vitamin D deficiency in regions with less exposure to sunlight [3]. In addition, clinical studies have reported cross-sectional associations between lower vitamin D levels and prevalent cardiovascular disease. The most important results come from a recently published prospective longitudinal study demonstrating that individuals with 25(OH)D levels below 37.5 nmol/l had a multivariable-adjusted hazard ratio of 1.62 for incident cardiovascular events compared with those with 25(OH)D levels of 37.5 nmol/l or greater [4].'Studies in knockout mice have confirmed that the absence of vitamin D-receptor activation leads to hypertension, left ventricular hypertrophy and also to disturbed blood coagulation.'Low levels of 25(OH)D are present in as many as a third to a half of otherwise healthy middle-aged to elderly adults. Data from the 1958 British Birth Cohort demonstrated that, duri...

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Low Vitamin D Status, High Bone Turnover, and Bone Fractures in Centenarians

Cited by 119 publications

References 54 publications

Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism

Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism

Calcium metabolism and vitamin D in the extreme longevity

Can Vitamin D Deficiency Impact Cardiovascular Health in the Elderly?

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