Effect of Age-Related Chronic Immobility on Markers of Bone Turnover

Abstract

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.

Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS)

“…A more marked resurgence of bone turnover has been previously observed in older men for some, but not all, bone turnover markers -mainly free and total deoxypyridinoline, and in some, but not all, cohorts -mainly in men over the age of 80 (1-4). Such a significant increase has been primarily observed in elderly men with impaired mobility and hormonal or nutritional insufficiencies (38)(39)(40), and may therefore not apply to the present cohort of relatively healthy communitydwelling men. Most of the variability in bone turnover rate could not be accounted for, even when combining age, lifestyle and key hormones of bone metabolism data.…”

Clinical application of biochemical markers of bone turnover

“…It is now widely accepted that the accelerated rate of bone loss seen after the menopause is mainly due to an uncoupling in bone turnover and an increase in bone resorption (26,27). Studies employing specific bone markers indicate that bone turnover continues to be increased (and to be associated with bone loss) during late menopause (28)(29)(30)(31)(32)(33). In some postmenopausal women (34), but particularly in the very elderly (35)(36)(37), this increase in bone turnover is often, but not always, found to be due to vitamin D and/or calcium deficiency and secondary hyperparathyroidism.…”

“…Together with the fact that high bone turnover may be sustained for long periods and bone loss may increase with age (44), these findings may provide a rationale for designing more effective intervention strategies. However, other factors such as age (see above), medication (6,18,(46)(47)(48)(49)(50)(51), immobilisation (32,35), thyroid function (52), co-morbidity (35) and the fracture itself (40,53,54) do influence bone metabolism and therefore need to be considered in the interpretation of biochemical data and their use in individual patients. Clearly, none of the biochemical markers of bone turnover has proven useful as a single diagnostic index of osteoporosis.…”

“…For example, markers of bone turnover may reflect changes in bone metabolism induced by oophorectomy (57,125), hyperparathyroidism (126,127), Paget's disease (128), physical exercise (129), immobilisation (32,130), alcoholism (131), smoking (132), vitamin D deficiency (33,35,37,133), chronic inflammatory bowel disease (134,135), chronic starvation (136), thyroid disorders (52,137) as well as the pharmacological effects of glucocorticosteroids (48,139,140), androgens (6,7,141), gonadotropin-releasing hormone agonists (142), warfarin (143), growth hormone or insulin-like growth factors (144). Bone turnover markers may be useful in the diagnosis and management of certain of the above conditions, but in most cases has not been rigorously examined.…”

Biomarkers of Bone Turnover: Potential, Challenges and Pitfalls from the Laboratory Point of view

“…Conversely, immobility exacerbates bone loss and increased bone resorption and CTX levels, as reduced mobility accelerates the bone loss due to aging and increase CTX and P1NP levels in elderly subjects (n=111) [21][22]. Moreover, BTMs are increased following a fracture, and subjects with increased frailty risk had significantly high levels of PINP, β-CTX and PTH as well as low levels of 25(OH)D [23,24].…”