title: Vitamin D insufficiency reduces the protective effect of bisphosphonate on ovariectomy-induced bone loss in rats.
abstract: The present study was carried out to obtain an experimental model of vitamin D (vit D) insufficiency and established osteopenia (experiment 1) to then investigate whether vit D status, i.e. normal or insufficient, interferes with bone mass recovery resulting from bisphosphonate therapy (experiment 2). Rats (n = 40) underwent OVX (n = 32) or a sham operation (n = 8). The first 15 days post-surgery, all groups were kept under fluorescent tube lighting and fed a diet containing 200 IU% vit D (+D). They were then assigned during an additional 45 days to receive either +D or a diet lacking vit D (-D) and kept under 12 h light/dark cycles using fluorescent or red lighting. Serum 25HOD was significantly lower in -D rats (P < 0.0001). The type of lighting did not induce differences in 25OHD, calcium (sCa), phosphorus (sP), bone alkaline phosphatase (b-AL), CTX, bone density or histology. No osteoid was observed in undecalcified bone sections. Experiment 2 (105 days): rats were fed either +D or -D according to experiment 1 and were treated with either placebo or 16 mug olpadronate (OPD)/100 g rat/week during the last 45 days. Whereas 25HOD was significantly lower (P < 0.0001) in -D/OPD than in +D/OPD rats, no significant differences in sCa, sP, b-AL or CTX were observed. OPD prevented the loss of lumbar spine (LS) and proximal tibia (PT) BMD and the decrease in bone volume (BV/TV) (P < 0.05) and in the number of trabeculae observed in untreated rats. However, +D/OPD animals presented significantly higher values of LS BMD, PT BMD and BV/TV than -D/OPD rats (P < 0.05). No osteoid was observed in undecalcified sections of bone. In summary, this is the first experimental study to provide evidence that differences in vit D status may affect the anticatabolic response to bisphosphonate treatment. However, the molecular mechanism through which vit D insufficiency reduces the effect of the aminobisphosphonate remains to be defined.
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Sección Osteopatías Médicas del Hospital de Clínicas J. de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Silvina R
authors.initials: SR
authors.lastname: Mastaglia
authors.forename: Gretel G
authors.initials: GG
authors.lastname: Pellegrini
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Mandalunis
authors.forename: Macarena M
authors.initials: MM
authors.lastname: Gonzales Chaves
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Friedman
authors.forename: Susana N
authors.initials: SN
authors.lastname: Zeni
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology; D001851:Bone Diseases, Metabolic / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy / Q000009:adverse effects*; D010710:Phosphates / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014807:Vitamin D / Q000008:administration & dosage / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications* / Q000473:pathology
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D010710:Phosphates; D014807:Vitamin D; D000469:Alkaline Phosphatase; D002118:Calcium