High fluoride and low calcium levels in drinking water is associated with low bone mass, reduced bone quality and fragility fractures in sheep

Abstract

SummaryChronic environmental fluoride exposure under calcium stress causes fragility fractures due to osteoporosis and bone quality deterioration, at least in sheep. Proof of skeletal fluorosis, presenting without increased bone density, calls for a review of fracture incidence in areas with fluoridated groundwater, including an analysis of patients with low bone mass.IntroductionUnderstanding the skeletal effects of environmental fluoride exposure especially under calcium stress remains an unmet need of critical importance. Therefore, we studied the skeletal phenotype of sheep chronically exposed to highly fluoridated water in the Kalahari Desert, where livestock is known to present with fragility fractures.MethodsDorper ewes from two flocks in Namibia were studied. Chemical analyses of water, blood and urine were executed for both cohorts. Skeletal phenotyping comprised micro-computer tomography (μCT), histological, histomorphometric, biomechanical, quantitative backscattered electron imaging (qBEI) and energy-dispersive X-ray (EDX) analysis. Analysis was performed in direct comparison with undecalcified human iliac crest bone biopsies of patients with fluoride-induced osteopathy.ResultsThe fluoride content of water, blood and urine was significantly elevated in the Kalahari group compared to the control. Surprisingly, a significant decrease in both cortical and trabecular bones was found in sheep chronically exposed to fluoride. Furthermore, osteoid parameters and the degree and heterogeneity of mineralization were increased. The latter findings are reminiscent of those found in osteoporotic patients with treatment-induced fluorosis. Mechanical testing revealed a significant decrease in the bending strength, concurrent with the clinical observation of fragility fractures in sheep within an area of environmental fluoride exposure.ConclusionsOur data suggest that fluoride exposure with concomitant calcium deficit (i) may aggravate bone loss via reductions in mineralized trabecular and cortical bone mass and (ii) can cause fragility fractures and (iii) that the prevalence of skeletal fluorosis especially due to groundwater exposure should be reviewed in many areas of the world as low bone mass alone does not exclude fluorosis.

The incorporation of fluoride and strontium in hydroxyapatite affects the composition, structure, and mechanical properties of human cortical bone

“…The deteriorated mechanical properties with aging and osteoporosis are in agreement with previous studies . Regarding the mechanical properties after fluoride treatment, in vitro studies have shown that the exposure of bone specimen to fluoride causes a reduction in bone strength, while in vivo animal studies have shown positive as well as negative effects of fluoride on biomechanical properties . For treatment with strontium, there is still disagreement as to whether the biomechanical properties of bone are altered by the incorporation of strontium into the bone mineral matrix.…”

“…Here, the F and SR treatment groups had significantly higher backscattered signal intensities in comparison to non‐treated osteoporotic bone resulting in a 7% increase in Ca mean and 5% increase in Ca peak, although these values were still lower than in the control group. Indeed, treatment of osteoporosis with fluoride is associated with a higher mineralization pattern and may even lead to fluorosis at high fluoride doses with an abnormal bone mineralization and enlarged mineral crystals . However, the results show that treatment with fluoride at a dose of < 20 mg/d partly antagonizes the decreased mineral content due to osteoporosis.…”

“…20,21 At the tissue level fluoride affects in vivo bone microstructure as well as the physiological hydroxyapatite matrix through alterations in the crystal size and the degree of mineralization influencing the mechanical properties of bone. [22][23][24] However, a direct comparison of the effectiveness of strontium ranelate and fluoride in osteoporosis treatment with a focus on the resulting mechanical properties of bone remains to be established. We hypothesized that both strontium ranelate and fluoride treatments affect the composition, structure, and mechanical properties of human cortical bone.…”

Intact Bone Vitality and Increased Accumulation of Nonmineralized Bone Matrix in Biopsy Specimens of Juvenile Osteochondritis Dissecans

“…We speculate that this lack of mineralization makes this bone segment more prone to mechanical stress, which may result in subchondral insufficiency fractures. ** References 2,4,16,32,34,43,45,50,52. Vol. 43, No.…”

Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals

“…The GLP-2R is expressed on osteoclasts, and its activation is believed to reduce catabolic activity of these cells [86]. Therefore, GLP-2 therapy may be useful in livestock production to improve bone health and prevent conditions such as osteopenic disease in swine or fluorosis, which is most common among cattle, horses, and sheep in fluoride-contaminated environments [107] and increases the incidence of bone fractures in sheep [108]. Benefits of GLP-2 for these conditions include both improved calcium uptake through its effects on increasing calcium transporter expression in the intestinal tract and its direct effects on reducing bone resorption.…”