Calcitonin Secretion in Postmenopausal Osteoporosis

Tiegs, Robert D.; Body, Jean‐Jacques; Wahner, Heinz W.; Barta, Joyce M.; Riggs, B. Lawrence; Heath, Hunter

doi:10.1056/nejm198504253121705

Cited by 134 publications

(29 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A significant correlation between IL-1 and years since menopause was also found in the entire untreated postmenopausal population (r = -0.50; P < 0.005). [8][9][10][11][12][13][14][15] years after menopause were divided into two groups, those whose IL-1 activity was above the upper normal limit (defined as the mean IL-1 activity of the premenopausal women plus 2 SD), and those with normal levels of IL-1. Based on this criterion, a significant difference (P = 0.002) was found between the two groups in the distribution of the nonosteoporotic and the osteoporotic subjects.…”

Section: Resultsmentioning

confidence: 99%

“…There are no consistent changes in the levels of endocrine resorption stimulators, parathyroid hormone and 1,25-dihydroxyvitamin D3 (9,10), and plasma calcitonin, an inhibitor of resorption, while lower in women than in men (11), is not remarkably diminished in postmenopause (12). These findings have suggested that estrogen may act by modifying the production of one or more of the local factors now known to influence remodeling events.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.

Pacifici

Rifas

McCracken

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

340

133

View full text Add to dashboard Cite

In previous studies, we showed that blood monocyte elaboration of interleukin 1 (IL-1), a known stimulator of bone resorption, was higher in osteoporotic patients with rapid bone turnover than in those with slow turnover and in nonosteoporotic subjects. Since an acceleration of bone loss following menopause contributes to the risk of osteoporosis in women, we have studied the effects of menopause and ovarian steroid treatment on IL-1 release by monocytes obtained from nonosteoporotic and osteoporotic women. IL-1 activity in the monocyte culture medium derived from untreated postmenopausal women (nonosteoporotic and osteoporotic) was higher than in the medium derived from either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy (r = -0.75; P < 0.005) and the osteoporotic (r = -0.61; P < 0.01) untreated postmenopausal women. The difference between the two slopes was significant at P < 0.05. Premenopausal IL-1 levels were achieved within 8 years of menopause in the nonosteoporotic, but not in the osteoporotic, subjects in whom increases were evident as long as 15 years after menopause. IL-1 also correlated inversely with vertebral mineral density (r = -0.37; P < 0.05), as measured by quantitative computed tomography. In prospective studies, treatment with estrogen/ progesterone for 1 month caused a substantial highly significant decrease in IL-1 activity in each of three nonosteoporotic and five osteoporotic women, confirming the apparent effect of hormone therapy observed in the cross-sectional analysis. Although a cause-effect relationship has not been established, it is our hypothesis, based on these data, that alterations in IL-1 production may underlie the postmenopausal acceleration in bone loss and its inhibition by ovarian steroids. Persistent elevation of IL-1 secretion appears to be a feature of postmenopausal osteoporosis.Postmenopausal osteoporosis is an extremely common disabling condition characterized by a reduced bone mass and a heightened risk of fracture (1). It stems in part from a dramatic acceleration of bone loss that begins in the perimenopausal period and lasts for 5-10 years thereafter (2-4). The bone loss is attributable to a defect in bone remodeling in which bone resorption is excessive (5).Although estrogen deficiency underlies (2-4) and estrogen therapy mitigates this defect (6-8), the nature ofthe estrogenresponsive resorption stimulus is unknown. There are no consistent changes in the levels of endocrine resorption stimulators, parathyroid hormone and 1,25-dihydroxyvitamin D3 (9, 10), and plasma calcitonin, an inhibitor of resorption, while lower in women than in men (11), is not remarkably diminished in postmenopause (12). These findings have suggested that estrogen may act by modifying the production of one or more of the local factors now known to influence remodeling events. Among the most potent of these is interleukin 1 (IL-1), one of seve...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.

Pacifici

Rifas

McCracken

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

340

133

View full text Add to dashboard Cite

show abstract

“…Group I consisted of five subjects aged [19][20][21][22][23] Statistical analysis. Data were normalized using a log-transformation for statistical analysis.…”

Section: Methodsmentioning

confidence: 99%

Relationship between whole plasma calcitonin levels, calcitonin secretory capacity, and plasma levels of estrone in healthy women and postmenopausal osteoporotics.

Reginster¹,

Deroisy²,

Albert³

et al. 1989

J. Clin. Invest.

View full text Add to dashboard Cite

The exact role of calcitonin (CT) in the pathogenesis of postmenopausal osteoporosis remains unknown. Whole plasma calcitonin (iCT) basal levels, metabolic clearance rate (MCR), and production rate (PR) of CT were measured in 9 premenopausal and 16 postmenopausal women, including 11 osteoporotics (OP). Basal iCT levels were statistically lower in postmenopausal women than in the premenopausal group (P < 0.01) and strongly correlated (r = 0.72; P < 0.001) with estrone circulating levels (El). MCR were similar in all groups. PR were similar in eugonadal women between 22 (mean±SD = 30.9±9.9 tg/d) and 37 yr (mean±SD = 25.5±11.1 ,ug/d) premenopausal women. In healthy postmenopausal women PR were reduced, but not significantly (mean±SD = 19.5±6.95 pg/d), whereas osteoporotic patients presented a highly significant reduction of CT PR (mean±SD = 9.8±4 gg/d) (P < 0.01). Because there is a strong relationship between El and PR (r = 0.64; P < 0.001), CT secretory capacity appears to be modulated by estrogen circulating levels. This modulation leads to a menopause-related decrease in iCT. In osteoporotics, an independent impairment of CT production drastically lowers PR and basal iCT levels. CT might be one of the determining factors in the pathogenesis of postmenopausal osteoporosis.

show abstract

“…However, although pharmacologic amounts of calcitonin prevent bone loss associated with osteoporosis, low circulating calcitonin is not a characteristic of osteoporosis. The opposite is apparently true: excessive skeletal calcium release such as that occurring with osteoporosis apparently stimulates calcitonin secretion and increases the concentration of calcitonin in plasma (Tiegs et al, 1985;McCarroll, 1993). Thus, the finding of decreased serum calcitonin with relatively high dietary zinc probably should not be considered undesirable.…”

Section: Discussionmentioning

confidence: 99%

A moderately high intake compared to a low intake of zinc depresses magnesium balance and alters indices of bone turnover in postmenopausal women

Nielsen

Milne

2004

Eur J Clin Nutr

View full text Add to dashboard Cite

Objectives: To determine whether moderately high or low intakes of zinc adversely affect the copper status of postmenopausal women to result in unfavorable changes in calcium and magnesium metabolism and other indicators of bone turnover. Design: After a 10-day equilibration period in which the diet provided 31.5 mmol (2 mg) Cu and 137.7 mmol (9 mg) Zn/8.4 MJ (2000 kcal), the subjects were randomly divided into two groups, with one group fed the basal diet supplemented to provide15.7 mmol (1 mg) Cu/8.4 MJ, and the other group fed the same diet supplemented to provide 47.2 mmol (3 mg) Cu/ 8.4 MJ. After equilibration, both groups were fed the basal diet with no zinc supplemented (provided 45.9 mmol [3 mg] Zn/ 8.4 MJ) for 90 days; this was followed by another 10-day equilibration period before the basal diet was supplemented with zinc to provide 811 mmol (53 mg)/8.4 MJ for 90 days. Setting: The metabolic unit of the Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA. Subjects: A total of 28 postmenopausal women recruited by advertisement throughout the United States of America. Among them, 25 women (64.9 þ 6.7 y) completed the study; 21 as designed. Results: The moderately high intake compared to the low intake of zinc increased the excretion of magnesium in the feces and urine, which resulted in a decreased magnesium balance. In the women fed low dietary copper, plasma osteocalcin was higher during the low-zinc than high-zinc dietary period. The urinary excretion of N-telopeptides was increased and the serum calcitonin concentration was decreased by high dietary zinc regardless of dietary copper. Conclusions: A moderately high intake of zinc (811 mmol/day; 53 mg/day) did not induce changes in copper metabolism that resulted in unfavorable changes in bone or mineral metabolism. However, low dietary zinc (45.9 mmol/day; 3 mg/day) apparently resulted in undesirable changes in circulating calcitonin and osteocalcin. As a moderately high intake of zinc decreased magnesium balance, further study of the possibility that a high intake of zinc is a health concern for individuals consuming less than the recommended amounts of magnesium is warranted.

show abstract

Calcitonin Secretion in Postmenopausal Osteoporosis

Cited by 134 publications

References 15 publications

Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.

Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.

Relationship between whole plasma calcitonin levels, calcitonin secretory capacity, and plasma levels of estrone in healthy women and postmenopausal osteoporotics.

A moderately high intake compared to a low intake of zinc depresses magnesium balance and alters indices of bone turnover in postmenopausal women

Contact Info

Product

Resources

About