Key Findings - Fluoride & Stress Fractures:

1) Due to its ability to increase bone mass in some areas of the skeleton, fluoride has been used as an experimental treatment for osteoporosis. However, despite 40 years of experimentation, fluoride remains an unapproved drug for this purpose (due to adverse side effects) and thus remains confined to experimental clinical trials.

2) One of the most widely acknowledged side effects of fluoride treatment is an increase in stress fractures (aka "microfractures") among the lower-limbs of the treated patients.

3) Fluoride-induced stress fractures have been reported in the femoral neck, thus explaining the increased incidence of spontaneous hip fractures among fluoride-treated patients.

Excerpts from the Scientific Literature - Fluoride & Stress Fractures in Clinical Trials: (back to top)

"Some histomorphometric studies have confirmed that accumulation of fluoride in certain bone sites worsens microfractures... It is now widely recognized that the lower limb pain syndrome (in fluoride-treated patients) is related to the presence of bone fissures."
SOURCE: Haguenauer D, et al. (2000). Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis. Osteoporosis International 11(9):727-38.

"We report here stress fractures of the lower limbs occurring in patients undergoing fluoride therapy for osteoporosis. Similar features have been reported by several authors. These stress fractures could not be prevented by calcium supplementation in most of our 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.

"In 19 of the 20 (fluoride-treated) women wtih the acute lower-extremity pain syndrome, a search was made for incomplete ('stress') fractures by roentgenography of the painful area at least two weeks after the onset of the pain. Eleven such fractures were identified by the radiologist... The incomplete fractures resembled the stress fractures reported after a skeletal overload from athletic activities and, like them, occurred almost entirely in weight-bearing bones."
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.

"The rate of peripheral stress fractures of 25.6% per year in the present study was more than three times the overall fracture rate of 7% per year in untreated, osteoporotic post-menopausal women. The fact that periarticular stress fractures were confined to the lower limbs suggests that the bone had become too weak to withstand weight bearing."
SOURCE: Schnitzler CM, et al. (1990). Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis. Clinical Orthopaedics (261):268-75.

"In four of the six hip fractures in this study, the history strongly suggested that the fracture occurred before the patient fell. The spontaneous character of the fracture in our patients, and in other reports, suggest that fluoride treatment probably increases the risk of stress fractures."
SOURCE: Hedlund LR, Gallagher JC. (1989). Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. Journal of Bone and Mineral Research 4:223-5.

"It is now believed that the articular pain occuring during fluoride therapy is the result of microfractures."
SOURCE: Pak CY. (1989). Fluoride and osteoporosis. Proceedings of the Society for Experimental Biology and Medicine 191: 278-86.

"Joint pain and swelling occur in about one third of treated patients. Although these features are generally attributed to rheumatic phenomena, such as synovitis or plantar fasciitis, it has been suggested that they are, in fact, due to juxtaarticular stress fractures. Until now this assertion has been based entirely on radiographic evidence. In the present paper we report the histologic features of one such lesion in a patient receiving fluoride, calcium, and 1a-vitamin D for postmenopausal osteoporosis."
SOURCE: Schnitzler CM, Solomon L. (1986). Histomorphometric analysis of a calcaneal stress fracture: a possible complication of fluoride therapy for osteoporosis. Bone 7: 193-8.

"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: 561-6.

"Periarticular pain and swelling during fluoride have usually been attributed to synovitis and our finding of synovial effusions in two such cases would seem to support this notion. However, in our patients passive movement of the affected joints did not aggravate the pain and examination of the synovial fluid revealed no sign of inflammation. We suggest that this is a sympathetic effusion secondary to juxta-articular stress fractures. Similarly, pain in the sole of the foot, usually ascribed to plantar fascitis, can be accounted for by calcaneal stress fractures. The arguments in favour of this explanation are persuasive: in our (as well as other) series, symptoms have been confined to the lower limbs, suggesting a mechanical rather than a 'rheumatological' cause; in each case pain was followed by the appearance of a radiodense band in the juxta-articular bone and in seven out of 17 instances there was a well-marked periosteal reaction. Radiographic signs of a stress fracture are unlikely to be present when the patient first complains of pain and in our cases they appeared 6-8 weeks after the onset of symptoms..."
SOURCE: Schnitzler CM, Solomon L. (1985). Trabecular stress fractures during fluoride therapy for osteoporosis. Skeletal Radioliology 14:276-9.

"An increased number of microfractures was found frequently in fluorotic bone. They were generally located in old bone with a high mineral-to-matrix concentration ratio... More frequent and abrupt variations in this ratio were found in fluorotic bone, and this probably increased the susceptibility of areas with a high ratio to microfractures."
SOURCE: Baylink DJ, Bernstein DS. (1967). The effects of fluoride therapy on metabolic bone disease. Clinical Orthopaedics and Related Research 55: 51-85.

Excerpts from the Scientific Literature - Stress Fracture as a Cause of Some Hip Fractures: (back to top)

"Stress fractures are part of a spectrum of structural inadequacy, spanning from a few asymptomatic microscopic fractures of trabeculae, which also occur in untreated individuals, to undisplaced stress fractures to displaced spontaneous fractures of the hip and long-bone shafts."
SOURCE: Schnitzler CM, et al. (1990). Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis. Clinical Orthopaedics (261):268-75.

"Orcel et al (1988) from France described 18 patients with spontaneous lower limb fractures, including 10 with hip fractures, of which three became complete and required surgery... The femoral neck was the most common site of stress fracture."
SOURCE: Gutteridge DH, et al. (1990). Spontaneous hip fractures in fluoride-treated patients: potential causative factors. Journal of Bone and Mineral Research 5(Suppl 1):S205-15.

"In four of the six hip fractures in this study, the history strongly suggested that the fracture occurred before the patient fell. The spontaneous character of the fracture in our patients, and in other reports, suggest that fluoride treatment probably increases the risk of stress fractures."
SOURCE: Hedlund LR, Gallagher JC. (1989). Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. Journal of Bone and Mineral Research 4:223-5.

Excerpts from the Scientific Literature - Fluoride & Spontaneous Bone Fracture:

"We report 11 fluoride-treated postmenopausal patients who developed spontaneous fractures of the femoral necks... [W]e believe that the available evidence strongly favors an association between spontaneous femoral fractures (stress and surgical) and NaF (sodium fluoride) plus Ca treatment under certain circumstances."
SOURCE: Gutteridge DH, et al. (1990). Spontaneous hip fractures in fluoride-treated patients: potential causative factors. Journal of Bone and Mineral Research 5 Suppl 1:S205-15.

"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.

"In four of the six hip fractures in this study, the history strongly suggested that the fracture occurred before the patient fell. The spontaneous character of the fracture in our patients, and in other reports, suggest that fluoride treatment probably increases the risk of stress fractures."
SOURCE: Hedlund LR, Gallagher JC. (1989). Increased incidence of hip fracture in osteoporotic women treated with sodium fluoride. Journal of Bone and Mineral Research 4:223-5.

"Thirteen cases of spontaneous fissure or fracture of the lower limbs observed in 8 patients under treatment with sodium fluoride are reported; 7 of these patients were being treated for osteoporosis... 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..."
SOURCE: 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.

"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."
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.

"Three or four of the fractures in the fluoride group appeared to be spontaneous hip fractures... 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.

"Spontaneous fractures are fairly frequent."
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.