Fluoride Treatment Increased Serum IGF-1, Bone Turnover, and Bone Mass, but Not Bone Strength, in Rabbits

Abstract

We hypothesized that fluoride partly acts by changing the levels of circulating calcium-regulating hormones and skeletal growth factors. The effects of oral fluoride on 24 female, Dutch-Belted, young adult rabbits were studied. The rabbits were divided into two study groups, one control and the other receiving about 16 mg fluoride/rabbit/day in their drinking water. After 6 months of fluoride dosing, all rabbits were euthanized and bone and blood samples were taken for analyses. Fluoride treatment increased serum and bone fluoride levels by over an order of magnitude (P < 0.001), but did not affect body weight or the following serum biochemical variables: urea, creatinine, phosphorus, total protein, albumin, bilirubin, SGOT, or total alkaline phosphatase. No skeletal fluorosis or osteomalacia was observed histologically, nor did fluoride affect serum PTH or Vitamin D metabolites (P > 0.4). BAP was increased 37% (P < 0.05) by fluoride; serum TRAP was increased 42% (P < 0.05); serum IGF-1 was increased 40% (P < 0.05). Fluoride increased the vertebral BV/TV by 35% (P < 0.05) and tibial ash weight by 10% (P < 0.05). However, the increases in bone mass and bone formation were not reflected in improved bone strength. Fluoride decreased bone strength by about 19% in the L5 vertebra (P < 0.01) and 25% in the femoral neck (P < 0. 05). X-ray diffraction showed altered mineral crystal thickness in fluoride-treated bones (P < 0.001), and there was a negative association between crystal width and fracture stress of the femur (P < 0.02). In conclusion, fluoride's effects on bone mass and bone turnover were not mediated by PTH. IGF-1 was increased by fluoride and was associated with increased bone turnover, but was not correlated with bone formation markers. High-dose fluoride treatment did not improve, but decreased, bone strength in rabbits, even in the absence of impaired mineralization.

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

“…The crucial question in the context of this review is whether or not it could have been predicted from preclinical studies, conducted as recommended in the WHO guidelines, that increases in bone mass would not be associated with a comparable increase in bone strength in osteoporotic patients treated with fluoride over a wide dose range. Overall analysis of the current preclinical studies indicates that fluoride does not improve bone strength in several animal models including rats, minipigs and rabbits [63][64][65], although it can increase spinal bone mass [63,65,66] as in the human, at least in the so-called good responders.…”

The Effect of Fluoride Treatment on Bone Mineral in Rabbits

“…This study is a continuation of a previous study examining the effect of high levels of fluoride consumption (100 ppm in the drinking water of young rabbits) on serum markers, bone turnover, and bone mechanical properties [1]. The focus of this work is the effect on bone mineral.…”

Bilateral atraumatic avulsion fracture of the calcaneal tubercle in osteomalacia during fluoride therapy-a case report

“…1996b, Ringe 1997) and thus to an increased fracture rate (Schnitzler andSolomon 1986, Orcel et al 1990). Patients with renal failure may develop osteomalacia (Turner et al 1997). Osteomalacia causes disturbed mineralization and thus raises the fracture rate.…”