Differente effects of Olpadronate in Osteopenic rats with a normal or deficient state of vitamin D. Prelimanary study

ZENI S, MASTAGLIA SR, MANDALUNIS P, DEGRANDI MC, SOMOZA J, FRIEDMAN S.

Davos, Suiza

Congreso; Seventh Workshop on Bisphosphonates from the laboratory to the patient; 2004

International Bone and Mineral Society

Different Effects of Olpadronate in Osteopenic Rats with a Normal or Deficient State of Vitamin D. Preliminary Study Susana Zeni,*, Silvina Mastaglia,* Patricia Mandalunis, María del C Degrandi,* Somoza Julia,* Silvia Friedman *Sección  Osteopatías Médicas-Hospital de Clínicas-Fac. de Medicina-UBA y Cátedra de Bioquímica General y Bucal. Facultad de Odontología. UBA y  Cátedra de Fisiología. Facultad de Odontología. UBA   Background: Ovariectomized (OVX) rats are often used as an experimental model to study estrogen deficiency as well as to test the efficacy of different therapies in preventing bone loss. Bisphosphonates (BPs) are useful antiresortiveagents to inhibit resorption in several bone diseases. Vitamin D insufficiency or deficiency has negative effects on skeletal metabolism. There is controversy related to the effect of BPs in vitamin D depletion state. Objective: The aim of the present preliminary study was to investigate if olpadronate (OPD) has different effects in recovery bone mass in OVX rats with established osteopenia and different vitamin D state. Material and Methods: A total of 24 female Wistar rats (250-300 g) were OVX and divided in three groups: 1) + VitD: animals fed with a synthetic diet that covered all adequate requirements, 2) _VitD (laking of dietary vitamin D and skin production): Animals were housed under red light and fed with the same synthetic diet without Vitamin D, 3)+/_VitD: these rats were laking of skin production and fed with dietary Vitamin D. During 60 days rats lost approximately 15% of bone mass, after that (To) all animals received during a 45-day period (Tf) 16 ug OPD/100 g rat weekly. Bone mineral density (BMD), 25OHvitamin D (ng/ml), bone alkaline phosphate (bALP) (mUI/ml) and serum CTX (ng/ml) were assessed at To and Tf and tibia histomorphometry was made at Tf. Results: Changes (Tf-To) in total skeleton (te), lumbar spine (ls), proximal tibia (pt) BMD (mg/cm2, bALP and sCTX were calculated (Table 1). Different letters indicated a p < 0.05. Histological sections of tibia in _VitD group evidenced greater thickness of metaphyseal cartilage and sealed trabeculae immediately below it. The presence of bone trabeculae defined osteoid surfaces. The +VitD group had greater bone volume and a decrease of the sealed trabeculae and osteoid surface compared to the _VitD group. Conclusion: Bone resorption inhibition, bone volume and positive changes in BMD were higher in the +VitD group suggesting that OPD effects is less beneficial in vitamin D deficient state     Table 1 BMDT BMDLS BMDPT BALP SCTX 25OHD(TF) + VITD + OPD 12F4A 7.4F3.0A 20.0F8.1A 1.2F3.1A _94.0F12.5A 59.0F3.5A _VITD + OPD 5F3A 1.2F2.0B 6.8F3.1B _0.3F3.3A _57.0F9.6B 9.2F0.8B +/_VITD + OPD 7F1A 5.5F3.1A 16.2F4.3A 2.1F2.8A _106F10.8A 58.0F3.2A