Abnormal bone mineralization after fluoride treatment in osteoporosis: A small-angle x-ray-scattering study

Abstract

Sodium fluoride treatment of osteoporosis is known to stimulate bone formation and to increase bone mass, but recent clinical trials failed to prove its antifracture effectiveness. The formation of bone with abnormal structure and, therefore, increased fragility is discussed as a possible explanation. Until now, however, exact information on the mineral structure of osteoporotic bone after fluoride treatment has been lacking. Bone biopsies were taken from three patients with postmenopausal osteoporosis before and after fluoride treatment (60 mg NaF/day for 1-2 years), from one patient with iatrogenic fluorosis, as well as from three normal controls. The mineral in these samples was investigated by a combination of backscattered electron imaging and small-angle x-ray scattering. Depending on the total dose of fluoride, an increasing amount of new bone is laid down on the surface of preexisting trabeculae. Its mineral structure is identical to that of heavy fluorosis and is characterized by the presence of additional large crystals, presumably located outside the collagen fibrils. These large crystals, which are not present in the controls or in osteoporotic bone before fluoride treatment, contribute to increase the mineral density without significantly improving the biomechanical properties of the bone. The possible success of fluoride treatment depends not only on the amount of newly formed bone but also on the rate of bone turnover. Indeed, as soon as significant amounts of fluoride are present, bone turnover leads to the replacement of old (normal) bone by new (pathologically mineralized) bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Infrared Assessment of Bone Quality: A Review

“…The important contribution of mineral maturity/crystallinity in determining bone strength may be appreciated in the case of fluoride-treated osteoporotic bone. In that instance, despite gains in BMD, bone eventually becomes fragile because of the crystallites' increased maturity/crystallinity due to the physical chemical effect of fluoride on biologic apatites [21,23,69,70].…”

“…Such a case would be bisphosphonates as they adsorb onto the apatitic surfaces, changing the surface properties, and affect the rate of mineral growth and dissolution . Other examples would be strontium [40,71] as it incorporates into the apatitic mineral, changing its dissolution characteristics and crystallite size and shape, and fluoride [21,23,69,70] as it incorporates into the apatitic mineral crystallites, making them larger, and greatly reduces the dissolution rate of these crystallites. As far as collagen properties are concerned, an example would be homocysteine [1,75] as it interferes with collagen enzymatic posttranslation modifications that occur after it has been synthesized and excreted by the osteoblast.…”

From diffraction to imaging: New avenues in studying hierarchical biological tissues with x-ray microbeams (Review)

“…Small-angle x-ray scattering has long been employed to study the size shape and arrangement of these mineral particles in human bone, 53,54 in particular, also in connection with bone diseases and treatment. 55,56 Two structural parameters are easily obtained from SAXS on bone using a pinhole camera with 2D detector ͓see, e.g., Fig. 2͑b͔͒: ͑i͒ from the azimuthally averaged SAXS intensity I͑q͒, the mean chord length ͑or T parameter͒ is obtained, which is directly related to the average thickness of the plate-shaped mineral particles, 53,57 and ͑ii͒ the elliptical shape of the SAXS isointensity contour ͓Fig.…”

Fluoride Exposure May Accelerate the Osteoporotic Change in Postmenopausal Women: Animal Model of Fluoride-induced Osteoporosis

“…The scientific justification for F therapy for osteoporosis, which induced irregular periosteal bone formation, ligament calcification, abnormal mineralization, and an increase of osteoid formation [29][30][31][32][33][34][35][36], is as follows: Concerning the high dose of F treatment, the increase of bone mineral density might be attributed to the pathological mineralization seen by an abnormal calcification and the presence of large crystals located outside the collagen fibrils [16,17,35,37]. This occurs because a high content of F ions absolutely inhibits the synthesis or activity of certain enzymes such as enolase and carbonic anhydrase [13,14,[38][39][40][41][42].…”