Fluoride Action Network

Clinical Trials: Fluoride Treatment & Bone Fracture in Osteoporosis Patients

Fluoride Action Network | April 2012 | By Michael Connett
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  • Due to its ability to increase bone mass, fluoride has been used as an experimental treatment for osteoporosis. The results, however, have generally been disastrous. Rather than prevent bone fractures in osteoporosis patients, fluoride therapy (at doses of 20-34 mg/day) was repeatedly found to increase fracture rates. One of the most common sites for fluoride-induced fracture has been the hip, specifically the femoral neck. Several clinical trials found that fluoride treatment caused the hip to “spontaneously” fracture — meaning the hip fractured in the absence of any physical trauma. Fluoride’s ability to cause spontaneous hip fracture is likely the result of fluoride-induced stress fractures, which have also been well documented in the clinical trials.

    Besides bone fracture, other reported side effects of fluoride treatment included gastrointestinal disorders, ‘lower-extremity pain syndrome’ (which, in some cases, may be the result of stress fractures), and osteomalacia. Based on this track record, the Food & Drug Administration has rejected fluoride therapy as an approved way of treating osteoporosis.

    Clinical Trials Finding Increased Fracture Rates Among Fluoride-Treated Patients

    “Vertebral fracture rates and peripheral bone density changes were surprising – and demonstrate that NaF administration is capable of increasing vertebral fracture rates and of increasing peripheral (nonspinal) bone loss. Thus our study demonstrates the potential for an anti-osteoporosis agent, under certain circumstances, to worsen a patient’s clinical state.”
    SOURCE: Gutteridge DH, et al. (2002). A randomized trial of sodium fluoride (60 mg) +/- estrogen in postmenopausal osteoporotic vertebral fractures: increased vertebral fractures and peripheral bone loss with sodium fluoride; concurrent estrogen prevents peripheral loss, but not vertebral fractures. Osteoporosis International 13:158-70.

    “We conducted an effectiveness meta-analysis to determine the efficacy of fluoride therapy on bone loss, vertebral and nonvertebral fractures and side effects in postmenopausal women…[A]lthough fluoride has an ability to increase bone mineral density at the lumbar spine, it does not result in a reduction in vertebral fractures. Increasing the dose of fluoride increases the risk of nonvertebral fractures and gastrointestinal side effects without any effect on the vertebral fracture rate.”
    SOURCE: Haguenauer D, et al. (2000). Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis. Osteoporosis International 11:727-38.

    “In this investigation, we found that after 5 years of fluoride treatment of osteoporotic patients, iliac crest trabecular bone strength was reduced by 46-56% compared with pretreatment biopsies. Also, 1 year of fluoride administration seemed to reduce bone strength by 17-30%, though this was not a significant finding… [T]he results of this study support the investigations that have found an increased rate of nonvertebral fractures, and a reduction in strength could well be a direct effect of fluoride on trabecular bone.”
    SOURCE: Sogaard CH, et al. (1994). Marked decrease in trabecular bone quality after five years of sodium fluoride therapy–assessed by biomechanical testing of iliac crest bone biopsies in osteoporotic patients. Bone 15: 393-99.

    “Bone fragility during fluoride therapy for osteoporosis was observed in 24 (37.5%) of 64 patients treated with sodium fluoride, calcium, and vitamin D for 2.5 years who developed episodes of lower-limb pain during treatment. Eighteen (28%) of these patients had clinical and roentgenographic features of 41 stress fractures and 12 new spinal fractures. There were 26 periarticular, six femoral neck, three pubic rami, three tibia and fibula, one greater trochanter, and two subtrochanteric fractures. Vertebral fractures appeared first, then periarticular, then femoral neck, and lastly long-bone shaft fractures. All fractures were spontaneous in onset. The peripheral fracture rate during treatment was three times that in untreated osteoporosis.”
    SOURCE: Schnitzler CM, et al. (1990). Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis. Clinical Orthopedics (261):268-75.

    Fluoride treatment was “associated with a significant three-fold increase in the incidence of nonvertebral fractures, both incomplete and complete…This increased rate of fracturing suggests that bone formed during fluoride therapy has increased fragility.”
    SOURCE: Riggs BL, et al. (1990). Effect of Fluoride treatment on the Fracture Rates in Postmenopausal Women with Osteoporosis. New England Journal of Medicine 322:802-809.

    “Using all 61 fluoride-treated patients, femur fractures/patient were significantly correlated to bone fluoride (p less than 0.05) and to age (p less than 0.05)… These results suggest that fluoride therapy may be implicated in the pathogenesis of hip fractures which may occur in treated patients despite a rapid, marked increase in bone mass.”
    SOURCE: Bayley TA, et al. (1990). Fluoride-induced fractures: relation to osteogenic effect. Journal of Bone and Mineral Research 5(Suppl 1):S217-22.

    “We report clinical and bone morphometric findings in 18 osteoporotic patients who experienced stress fractures during fluoride therapy… Fluoride appears to be a key factor in the pathogenesis of stress fractures, and may be associated with increased trabecular resorption in some treated patients.”
    SOURCE: Orcel P, et al. (1990). Stress fractures of the lower limbs in osteoporotic patients treated with fluoride. Journal of Bone and Mineral Research 5(Suppl 1): S191-4.

    “[T]he six hip fractures occurring in patients receiving fluoride during 72.3 patient years of treatment is 10 times higher than would be expected in normal women of the same age. The probability of observing six fractures in 2 years is extremely small (0.0003). In four of the hip fracture cases, the history suggested a spontaneous fracture. These findings suggest that fluoride treatment can increase the risk of hip fracture in osteoporotic women.”
    SOURCE: Hedlund LR, Gallagher JC. (1989). Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. Journal of Bone and Mineral Research 2:223-5.

    “Thirteen cases of spontaneous fissure or fracture of the lower limbs observed in 8 patients under treatment with sodium fluoride are reported… Fluor seems to be responsible for the fissures which cannot be avoided by calcium and/or vitamin D intake… When such fissures occur, fluoride therapy must be discontinued and the limb put at rest…”
    Orcel P, et al. (1987). [Spontaneous fissures and fractures of the legs in patients with osteoporosis treated with sodium fluoride]. Presse Med 16:571-5.

    “How fluoride can produce stress microfractures is unclear. That they are complications of fluoride therapy is clear, as there were no microfractures in the 101 patients in the calcium-treated group.”
    SOURCE: O’Duffy JD, et al. (1986). Mechanism of acute lower extremity pain syndrome in fluoride-treated osteoporotic patients. American Journal of Medicine 80: 561-566.

    “[T]he increased number of new crush fractures of the spine during the first year of treatment raise the possibility of fluoride-induced microfractures.”
    SOURCE: Dambacher MA, et al. (1986). Long-term fluoride therapy of postmenopausal osteoporosis. Bone 7: 199-205.

    “Two patients with moderate renal failure sustained spontaneous bilateral hip fractures during treatment with fluoride, calcium, and vitamin D for osteoporosis….As bilateral femoral neck fractures are very rare these data suggest a causal link between fractures and fluoride in patients with renal failure. Thus fluoride should be given at a lower dosage, if at all, to patients with even mild renal failure.”
    SOURCE: Gerster JC, et al. (1983). Bilateral fractures of femoral neck in patients with moderate renal failure receiving fluoride for spinal osteoporosis. British Medical Journal (Clin Res Ed). 287(6394):723-5.

    “During treatment bone pain increased and three further vertebral compression fractures occurred.”
    SOURCE: Compston JE, et al. (1980). Osteomalacia developing during treatment of osteoporosis with sodium fluoride and vitamin D. British Medical Journal 281: 910-911.

    “Fractures and exacerbation of arthrosis were more frequent in the fluoride group…The many fractures in the fluoride group, 14 during treatment and the following month as against 6 among the controls, were surprising. Three or four of the fractures in the fluoride group appeared to be spontaneous hip fractures. In the past fractures have not been regarded as being caused by fluoride but as resulting from prolonged osteoporosis before treatment. We believe that the fluoride treatment here was probably partly responsible for the fractures in our cases.”
    SOURCE: Inkovaara J, et al. (1975). Phophylactic fluoride treatment and aged bones. British Medical Journal 3: 73-74.