Octreotide Abolishes the Acute Decrease in Bone Turnover in Response to Oral Glucose

Abstract

Feeding or oral intake of glucose results in an acute suppression of bone turnover. This does not appear to be mediated by insulin. Several gastrointestinal hormones modulate bone turnover in vitro and may mediate this response. We examined whether inhibiting the production of gastrointestinal hormones using octreotide could block glucose-mediated suppression of bone turnover. Fifteen subjects were each studied on four occasions in a randomized, single-blind, crossover study after receiving 1) oral placebo, iv saline; 2) oral glucose, iv saline; 3) oral glucose, iv octreotide; or 4) iv octreotide alone. We measured serum C-terminal telopeptide of type I collagen, urinary N-terminal telopeptide of type I collagen, osteocalcin, procollagen type I N-terminal propeptide, PTH, insulin, ionized calcium, and glucose over 4 h. All bone turnover markers decreased significantly after oral glucose (P < 0.001). At 120 min serum C-terminal telopeptide decreased by 45 +/- 2%, urinary N-terminal telopeptide by 31 +/- 7%, osteocalcin by 16 +/- 1%, and procollagen type I N-terminal propeptide by 8 +/- 1%. There was no significant decrease in bone turnover in response to oral glucose during octreotide infusion. Octreotide alone resulted in a significant increase in all bone turnover markers (P < 0.05) and PTH (P < 0.01). We conclude that octreotide completely abolishes the bone turnover response to glucose intake and increases PTH secretion. The apparent bone turnover response to feeding is probably mediated by an octreotide-inhibitable endocrine factor.

Effect of fasting versus feeding on the bone metabolic response to running

“…No effect of feeding on OC is consistent with previous studies [10][11][12], although others report decreases following the ingestion of glucose [13] or a meal [14]. Similar decreases in PINP occur after a meal [14] and glucose [13] ingestion, which may explain why PINP was approximately 10% lower in FED at 10:15.…”

“…Calcium ingestion also decreases resting P-CTX [41,42], although the mechanism for this effect is different, since changes in PTH do not explain the reduction in P-CTX following macronutrient ingestion [13]. Our meal contained 116 mg of calcium so we cannot exclude an effect on resting P-CTX, although this was only one third of the quantity (344 mg) shown to suppress both PTH and P-CTX [41] and we showed no significant effect of feeding on PTH.…”

“…Fasting attenuates the circadian variation in the C-terminal telopeptide region of collagen type 1 (P-CTX), a specific marker of bone resorption, while feeding suppresses resting P-CTX within 1 h and, after 2-3 h, concentrations are decreased by -50% [10][11][12][13]. In contrast, bone formation is largely unresponsive to nutrient ingestion [10][11][12]14].…”

“…Changes in parathyroid hormone (PTH) might be one such link, with concentrations being decreased following nutrient ingestion [13] and increased promptly with endurance exercise 6 [15,19,31]. Similarly, both leptin and ghrelin concentrations change markedly following feeding, with ghrelin decreasing [32] and leptin increasing [33], and both respond to exercise [34,35].…”

Successes Achieved and Challenges Ahead in Translating Biomarkers into Clinical Applications

“…The diurnal variation of serum osteocalcin is higher perhaps due to the fact it reflects both bone formation and bone resorption. Food intake has a lower effect on bone formation markers than on bone resorption markers (52).…”