Fluoride Action Network


Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget’s disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.


… Osteomalacia may be drug-induced (fluoride or etidronate) or the result of aluminum exposure in parenteral nutrition or hemodialysis. Clinical features are pain, fissures, and fractures, which may occur after minimal trauma (61) …

B. Abnormal mineral: fluorosis
The effects of fluoride on bone tissue depend on the cumulative dose: at very low dose, less than 1.5 mg F/d, fluoride prevents the development of dental caries; at doses of about 23 mg F/d, fluoride was proposed in the treatment of osteoporosis but no beneficial effects on the fracture rate were observed (67, 68). Skeletal fluorosis results from a prolonged ingestion of fluoride causing bone pain, stiffness, and rigidity and possible deformities of the spine and limbs (69).

Despite the increased bone tissue mass, the bone strength is reduced due to several abnormalities in mineral. The femoral and lumbar compressive strength of fluoride-treated rats is lower than controls (70, 71), and the fluoride treatment increases BMD in ovariectomized rats but decreases bone strength and stiffness (72). In vitro, fluoride exposure of mouse femora induces reductions in ultimate load and rigidity and an increase in ductility (73).

Histomorphometric analysis of iliac crest biopsies from patients with fluorosis shows that osteosclerosis is the result of unbalanced coupling in favor of bone formation (Fig. 5A). Mineralization defects are present in calcified tissue or around the osteocytic lacunae (Fig. 5B), and some area of woven bone may be observed but the bone texture is mainly lamellar (74). Despite an increased bone mass, fluoride treated mice have decreased bone strength (71).

Fluoride induces the production of an altered organic matrix and reduced mineralization. Some modifications of the amino acid composition of collagen (decreased hydroxyproline and lysine residues, increased proline residues) and of collagen cross-links disturb the mineralization process and consequently reduce the bone strength (75). Fluoride is incorporated into the crystalline lattice of hydroxyapatite, making the lattice more stable and less soluble and increasing the crystallinity of the bone mineral. The effect of fluoride on the crystal size is controversial (74, 76). In fluoride-treated rabbits, the length of hydroxyapatite crystals is unchanged, but the width is increased (77). Measured by quantitative microradiography, the mean degree of mineralization in skeletal fluorosis is decreased, but the intraindividual heterogeneity index of mineralization reflecting variation of the secondary mineralization is normal (78). In bone from fluoride-treated osteoporotic women and fluorotic patients, xray scattering shows crystals too large to be located inside the collagen fibrils (79). A tissue with a large amount of extrafibrillar mineralization is probably harder but more brittle. In addition, fluoride alters the interface between mineral and collagen that may influence the mechanical properties of bone (80).


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