Abstract
Objectives: Intake of multivitamin preparations is very common in developed countries. However, excessive intake of vitamin A was associated with increased bone fragility.
The aim of this study was to determine if chronic administration of the active metabolite of vitamin A all-trans-retinoic acid (ATRA) in slight excess is associated with changes of bone turnover and density in intact and castrated mice. Method: Three mo old male mice (C57B1/6) intact and castrated were injected intraperitonealy with 10 mg/kg/d of the ATRA or vehicle (control) once daily for 3 wk.
The bone density, ash weights, calcium, and phosphorus content of the femur were measured. Plasma tartrate-resistant acid phosphatase (Tr-ACP) and serum bone alkaline phosphatase (B-ALP) were determined.
Results: ATRA decreased bone density in both groups; however, this effect was more pronounced in castrated animals (1.487 +/- 0.04 to 1,360 +/- 0.05 g/cm(3)) than in intact mice (1.570 +/- 0.03 to 1.510 +/- 0.03 g/cm(3)). Bone density correlated with decreased B-ALP and increased Tr-ACP in ATRA-treated mice.
ATRA treatment led to significantly lower thickness of cortical bone both in the intact and castrated animals. Conclusion: Our results indicate that repeated administration of ATRA in slight excess leads to significant bone loss both in intact and castrated mice.
This effect was more pronounced in testosterone-deficient animals. Testosterone deficiency as occurs following castration may sensitize the bone to resorption mediated by ATRA.
Therefore, chronic vitamin A administration may be a risk factor for osteoporosis, especially in older and testosterone-depleted subjects.