Mechanism of circadian variation in bone resorption1
Introduction
Osteoporosis is a serious and common disease that occurs worldwide.3 The single most important risk factor for osteoporosis is estrogen deficiency, and it has been estimated that up to one third of postmenopausal women will be affected if left untreated.3 A primary event leading to osteoporotic bone loss is the increase in bone turnover associated with menopause. The acute increase in bone resorption seen with circadian variation takes place with a peak in the early morning, and the lowest level in the afternoon.18 This variation is independent of gender, age, and stage of osteoporosis, although an elevated baseline level is seen in postmenopausal women.5, 6, 12, 18, 19 It is also independent of physical activity, thus 3 days of bed-rest showed no change in variation in premenopausal women.19 In some studies, circadian variation in plasma cortisol has been assessed as a possible factor. Neither cortisol-insufficient individuals substituted intermittently with cortisol to eliminate circadian variation17 nor cortisol-clamp studies in healthy postmenopausal women8 demonstrated any influence on circadian variation in bone resorption. Parathyroid hormone (PTH)-clamp studies in pre- and postmenopausal women showed that circadian variation in bone turnover is also independent of serum PTH concentration.10 Recently, one study of premenopausal women demonstrated that circadian variation in bone resorption, as measured by urinary excretion of C-telopeptide fragments of collagen type 1 (CTx) degradation, was significantly diminished during fasting.16 Therefore, we designed a series of studies to elucidate the possible effects of components of food intake upon circadian variation in markers of bone turnover.
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Subjects and methods
All studies were approved by the local ethics committee and informed consent was obtained for all subjects. The participants had free access to mineral water throughout the investigation. They were weighed with their clothes on, but without shoes, using the same scale. Height was measured using a Harpenden stadiometer, also without shoes.
Results
Study I (study of bone turnover during OGTT, IVGTT, normal diet, and fasting). Baseline characteristics of the women are presented in Table 1. OGTT induced an acute decrease of 50% in s-CTx, which was highly significant after 1 h, fully expressed after 2 h (p < 0.001 at both timepoints after correction for fasting), and reversed to baseline after 6 h (Figure 1A). An identical decrease was seen in the normal diet group (p < 0.001 at 2 h after correction for fasting), but the decrease was
Discussion
These experiments show that the majority of the variation observed in biochemical markers of bone resorption over the day and night is not circadian but rather induced by food intake, and that this response is independent of gender and menopausal status. Separate intake of glucose, protein, or fat all led to an equal decrease in bone resorption. Our investigation of the influence of insulin on acute control of bone resorption found that variation of this parameter induced only a portion of the
Acknowledgements
The authors thank all participants and laboratory technicians for their hard work and the Danish affiliate of Eli Lilly for supplying us with insulin.
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2022, Journal of Clinical and Translational EndocrinologyCitation Excerpt :Previous data suggest that the bone forming osteoblasts and bone resorbing osteoclasts are responsive to consumption of macronutrients [39], resulting in a shift in the balance between bone formation and resorption, predominantly by decreasing bone resorption [29]. Consumption of a fixed amount of carbohydrate (75 g of glucose) in adults results in a significant reduction in CTX, a well-characterized biomarker of bone resorption, by 120 mins following ingestion [7,9,10]. We also found significant decreases in CTX following glucose ingestion in our study, as demonstrated by a median CTX-%Δ0-120min of about –32% by min 120, which is lesser in magnitude than the approximately 50% reduction in CTX by min 120 of OGTT that has been consistently reported previously in healthy adults [7,9,10].
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Data from studies contained in this report were submitted in abstract form at the 22nd meeting of the American Society of Bone and Mineral Research, Toronto, Ontario, Canada, September 2000.