Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: Evidence of an age-related intestinal resistance to 1,25-dihydroxyvitamin D action

Richard Eastell, Alfred L. Yergey, Nancy E. Vieira, Sandra L. Cedel, Rajiv Kumar, B. Lawrence Riggs

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Abstract

We studied the mechanism of impaired calcium absorption with aging in 51 healthy women whose ages ranged from 26 to 88 years. Serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D, mean of four measurements per subject] increased with age by 22% (P < 0.05) but, by split-point analysis, plateaued or decreased slightly after age 65. In a subset of 20 subjects, [1H]1,25-(OH)2D1 kinetic analysis showed that this increase with age resulted from both increased production and decreased metabolic clearance of 1,25-(OH)2D. Despite the increase in serum 1,25-(OH)2D concentration, true calcium absorption did not change with age. The expected inverse correlation between true fractional calcium absorption and dietary calcium intake, however, was easily demonstrated (r = 0.66, P < 0.001). Serum intact parathyroid hormone (PTH) increased with age by 35% (P < 0.02) and serum bone gla protein (BGP, osteocalcin) increased by 47% (P < 0.001); the increases in serum PTH and serum BGP were directly correlated (r = 0.32, P < 0.05). The data are consistent with the following hypothetical model: (1) intestinal resistance to 1,25-(OH)2D action accounts for the increase in serum 1,25-(OH)2D concentrations with aging with no change in true calcium absorption; (2) this results in a compensatory increase in PTH secretion and in 1,25-(OH)2D production that prevents true calcium absorption from decreasing; (3) the previously described defect in 25-hydroxyvitamin D (25-OHD) 1α-hydroxylase activity in aging animals and humans acccounts for the leveling off in serum 1,25-(OH)2D concentration after age 65 years; and (4) the secondary hyperparathyroidism leads to increased bone turnover and thus contributes to age-related bone loss.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalJournal of Bone and Mineral Research
Volume6
Issue number2
StatePublished - Feb 1991

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Vitamin D
Calcium
Serum
Parathyroid Hormone
Osteocalcin
Dietary Calcium
Secondary Hyperparathyroidism
Bone Remodeling
Mixed Function Oxygenases
1,25-dihydroxyvitamin D
Osteoporosis
Blood Proteins

ASJC Scopus subject areas

  • Surgery

Cite this

Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women : Evidence of an age-related intestinal resistance to 1,25-dihydroxyvitamin D action. / Eastell, Richard; Yergey, Alfred L.; Vieira, Nancy E.; Cedel, Sandra L.; Kumar, Rajiv; Riggs, B. Lawrence.

In: Journal of Bone and Mineral Research, Vol. 6, No. 2, 02.1991, p. 125-132.

Research output: Contribution to journalArticle

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abstract = "We studied the mechanism of impaired calcium absorption with aging in 51 healthy women whose ages ranged from 26 to 88 years. Serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D, mean of four measurements per subject] increased with age by 22{\%} (P < 0.05) but, by split-point analysis, plateaued or decreased slightly after age 65. In a subset of 20 subjects, [1H]1,25-(OH)2D1 kinetic analysis showed that this increase with age resulted from both increased production and decreased metabolic clearance of 1,25-(OH)2D. Despite the increase in serum 1,25-(OH)2D concentration, true calcium absorption did not change with age. The expected inverse correlation between true fractional calcium absorption and dietary calcium intake, however, was easily demonstrated (r = 0.66, P < 0.001). Serum intact parathyroid hormone (PTH) increased with age by 35{\%} (P < 0.02) and serum bone gla protein (BGP, osteocalcin) increased by 47{\%} (P < 0.001); the increases in serum PTH and serum BGP were directly correlated (r = 0.32, P < 0.05). The data are consistent with the following hypothetical model: (1) intestinal resistance to 1,25-(OH)2D action accounts for the increase in serum 1,25-(OH)2D concentrations with aging with no change in true calcium absorption; (2) this results in a compensatory increase in PTH secretion and in 1,25-(OH)2D production that prevents true calcium absorption from decreasing; (3) the previously described defect in 25-hydroxyvitamin D (25-OHD) 1α-hydroxylase activity in aging animals and humans acccounts for the leveling off in serum 1,25-(OH)2D concentration after age 65 years; and (4) the secondary hyperparathyroidism leads to increased bone turnover and thus contributes to age-related bone loss.",
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