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Responsiveness to 1,25-dihydroxyvitamin D3 is reduced in lymphocytes from osteoporotic women
R Koren1, A Ravid, U A Liberman
1Metabolic Diseases Unit, Beilinson Medical Center, Petah Tikva, Israel.
Abstract:
The purpose of this work was to test the hypothesis that reduced responsiveness of target organs to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is associated with osteoporosis. Peripheral blood mononuclear (PBM) cells have been previously shown to be a valid model for the action of 1,25(OH)2D3 on its classic target organs in various pathologic and physiologic situations. The responsiveness of lymphocytes to the hormone can be assessed by the extent of inhibition it exerts on the proliferative response to mitogenic lectins. A group of 39 postmenopausal women, at least 10 years after the menopause, participated in the study. Osteoporosis, defined as the presence of at least one nontraumatic vertebral crush fracture, was diagnosed in 19 subjects. Mitogenesis of PBM cells stimulated by phytohemagglutinin and cultured for 72 h in the presence or absence of 1,25-(OH)2D3 (0.03-1 nmol/liter) was assessed by [3H]thymidine incorporation during a 4 h pulse. The maximal inhibitory effect of 1,25-(OH)2D3 at saturating concentration (1 nM/liter) was 74.6 +/- 2.8% (mean +/- SEM) for normal compared to 65.3 +/- 2.9% for osteoporotic women (P = 0.015). The geometric mean of the ED50 values of 1,25-(OH)2D3 was 60% higher in the osteoporotic than in the normal group (P = 0.035). Our data are consistent with the notion that reduced responsiveness of target organs to 1,25-(OH)2D3 is associated with osteoporosis.
Insights
Postmenopausal women with osteoporosis show reduced target organ responsiveness to 1,25-dihydroxyvitamin D3. This vitamin D insensitivity may contribute to the development of osteoporosis in this population.
Area of Science:
- Endocrinology
- Bone Biology
- Immunology
Background:
- Osteoporosis is a significant health concern, particularly in postmenopausal women.
- Vitamin D plays a crucial role in calcium homeostasis and bone health.
- Reduced responsiveness to vitamin D metabolites may be implicated in osteoporosis pathogenesis.
Purpose of the Study:
- To investigate the association between reduced target organ responsiveness to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and osteoporosis.
- To determine if peripheral blood mononuclear (PBM) cells serve as a valid model for assessing vitamin D action in osteoporosis.
Main Methods:
- Studied 39 postmenopausal women, with 19 diagnosed with osteoporosis.
- Assessed lymphocyte responsiveness to 1,25-(OH)2D3 by measuring inhibition of mitogenic lectin-stimulated proliferation.
- Quantified [3H]thymidine incorporation in PBM cells cultured with varying concentrations of 1,25-(OH)2D3.
Main Results:
- Osteoporotic women exhibited a significantly lower maximal inhibitory effect of 1,25-(OH)2D3 on PBM cell proliferation (65.3%) compared to normal women (74.6%).
- The half-maximal effective concentration (ED50) for 1,25-(OH)2D3 was 60% higher in osteoporotic women, indicating reduced sensitivity.
- These findings suggest a diminished responsiveness of target cells to 1,25-(OH)2D3 in individuals with osteoporosis.
Conclusions:
- Reduced target organ responsiveness to 1,25-(OH)2D3 is associated with postmenopausal osteoporosis.
- PBM cells represent a viable model for studying vitamin D action in the context of osteoporosis.
- These results support the hypothesis linking vitamin D insensitivity to the development or progression of osteoporosis.