It is well established that fluoride exposure can increase bone formation by increasing the proliferation of osteoblasts. Less clear is fluoride’s impact on bone resorption and the cells (osteoclasts) that resorb bone. Many have assumed that fluoride’s main effect on bone resorption and osteoclasts is an inhibitory one (i.e., less bone resorption). While evidence does indicate that fluoride can inhibit osteoclasts and bone resorption, evidence also indicates that fluoride can increase osteoclast activity and bone resorption. While it is commonly assumed that much higher doses of fluoride are required to increase bone resorption than to increase bone formation.
Fluoride, Osteoclasts, & Bone Resoprtion:
“An iliac crest bone biopsy revealed an increased amount of thick unmineralized osteoid as well as a large number of osteoclasts and associated resorption cavities, consistent with osteomalacia.”
SOURCE: Hallanger Johnson JE, et al. (2007). Fluoride-related bone disease associated with habitual tea consumption. Mayo Clinic Proceedings 82(6):719-24.
“Osteoclasts were readily seen eroding bone. . . . Bone fluoride analysis showed 18 times the normal level of fluoride, 1.8%. Skeletal fluorosis was diagnosed.”
SOURCE: Kurland ES, et al. (2007). Recovery from skeletal fluorosis (an enigmatic, American case). J Bone Miner Res. 22(1):163-70.
“We observed osteoclasts resorbing bone beneath osteoid seams, and fragments of osteoid isolated in the bone marrow. This type of resorption beneath unmineralized bone matrix is often observed in osteomalacia, particularly that caused by renal abnormalities and associated secondary hyperparathyroidism.”
SOURCE: Lundy MW, et al. (1995). Histomophometric analysis of iliac crest bone biopsies in placebo-treated versus fluoride-treated subjects. Osteoporosis International 5:115-129.
“Although some authors have suggested that the resorption observed in skeletal fluorosis is due to secondary hyperparathyroidism in humans and in fluoride-treated animals, others have found no effect of fluoride on parathyroid mass or serum parathyroid levels in animal studies.”
SOURCE: Lundy MW, et al. (1995). Histomophometric analysis of iliac crest bone biopsies in placebo-treated versus fluoride-treated subjects. Osteoporosis International 5:115-129.
“While the stimulatory effects of fluoride on bone formation have been well described, its effects on bone resorption is less well understood.”
SOURCE: Grynpas MD, et al. (1994). Bone mineralization and histomorphometry in biopsies of osteoporotic patients treated with fluoride. Cells and Materials 4: 287-297.
“If calcium is deficient, mineralization defects will occur, and bone resorption may be enhanced.”
SOURCE: Mithal A, et al. (1993). Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiology 22: 257-61.
“While only two pretreatment biopsies are available and showed minimal tunneling, we have never seen this degree of cortical porosity and resorption in biopsies in numerous similar untreated patients. We believe these latter important structural changes to be fluoride related.”
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.
“We observed increased trabecular resorption on biopsies performed at the time of the stress fracture despite calcium supplementation. Schnitzler and Solomon also found excessive resorption on biopsies taken at the site of the stress fracture and an iliac crest in a patient who a calcaneal stress fracture during fluoride treatment. Morover, when compared with the resorption parameters of a group of fluoride-treated patients without stress fracture analyzed in our laboratory, the values found in our patients with stress fracture were markedly increased.”
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.
“Histologic description of fluorotic bone generally includes increased osteoid and mineralized bone, disordered lamellar structure, thickened trabeculae and cortical bone, and increased areas of resorption.”
SOURCE: Fisher RL, et al. (1989). Endemic fluorosis with spinal cord compression. A case report and review. Archives of Internal Medicine 149: 697-700.
“Our findings suggest that the optimal concentration of fluoride that increases bone resorption is higher than the concentration that increases formation. If this is correct, the effects of fluoride on bone formation and resorption may be mediated through different mechanisms and may be dissociable.”
SOURCE: Turner RT, et al. (1989). The effects of fluoride on bone and implant histomorphometry in growing rats. Journal of Bone and Mineral Research 4: 477-484.
“both skeletal formation and resorption appear to be increased following NaF administration.”
SOURCE: Marie PJ, Hott M. (1988). Short-term effects of fluoride and strontium on bone formation and resorption in the mouse. Metabolism 35: 547-551.
“In contrast to longer term treatment with NaF, short-term NaF supplementation did not increase the osteoclastic bone resorption whereas bone matrix formation was stimulated. Increased bone formation with unchanged bone resorption led to a significant augmentation of the trabecular bone volume after only four weeks of treatment.”
SOURCE: Marie PJ, Hott M. (1988). Short-term effects of fluoride and strontium on bone formation and resorption in the mouse. Metabolism 35: 547-551.
“In the present study, increases in resorptive and formative surfaces were of the same magnitude.”
SOURCE: Kragstrup J, et al. (1984). Experimental osteo-fluorosis in the domestic pig: a histomorphometric study of vertebral trabecular bone. Journal of Dental Research 63: 885-889.
“In the present study, the most significant alteration as a result of fluoride ingestion during three successive pregnancies and lactations was the dramatic loss of bone from the interior of the shaft. The bone was clearly histologically osteoporotic as evidenced by the numerous large resorption cavities, and bone remodeling occurred in the form of secondary Haversian systems. In addition, extensive resorption was characteristic of the metaphyseal trabeculae and of the endosteal surface.”
SOURCE: Ream LJ, et al. (1983). Fluoride ingestion during multiple pregnancies and lactations: microscopic observations on bone of the rat. Virchows Arch [Cell Pathol] 44: 35-44.
“[S]upplementary calcium… prevents the increase in bone resorption which occurs when sodium fluoride is given alone.”
SOURCE: Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393.
“Osteoclastic resorptive activity was increased (p <.001), but no evidence of hyperparathyroidism was noted.”
SOURCE: Vigorita VJ, Suda MK. (1983). The microscopic morphology of fluoride-induced bone. Clinical Orthopaedics and Related Research 177:274-282.
“conflicting results are common although most studies indicate that both formation and resorption are increased.”
SOURCE: Ream LJ. (1981). The effects of short-term fluoride ingestion on bone formation and resorption in the rat femur. Cell and Tissue Research 221: 421-430.
“First, the predominant effect of fluoride on bone is osteoblastic stimulation. Second, chronic ingestion of fluoride impairs mineralization of newly formed bone matrix and, at times, increases bone resorption…”
SOURCE: Riggs BL, et al. (1980). Treatment of primary osteoporosis with fluoride and calcium: Clinical tolerance and fracture occurrence. Journal of the American Medical Association 243(5): 446-449.
“As for the enlarged lacunae, the increase in their size was found to be caused by perilacunar resorption…”
SOURCE: Baud CA, et al. (1978). Value of the bone biopsy in the diagnosis of industrial fluorosis. Virchows Archiv A. Pathological Anatomy and Histology 380: 283-97.
“In several patients we failed to notice evidence of typical sclerosis in the radiogram. Instead, the picture of so-called ‘hypertrophic atrophy’ was found… It is likely that a previously existing osteoporosis is superimposed upon fluorosis or the predominance of the fluoride-induced bone resorption in conjunction with thickening of the statically loaded bone structure may be responsible.”
SOURCE: Franke J, et al. (1975). Industrial fluorosis. Fluoride 8: 61-83.
“All but one of the patients showed an increase in bone surfaces lined by osteoid and in these eight patients resorption of bone was the most striking finding…”
SOURCE: Faccini JM, Teotia SPS. (1974). Histopathological assessment of endemic skeletal fluorosis. Calcified Tissue Research 16: 45-57.
“Dental x-rays revealed resorption of the alveolar bone around the roots of the teeth as a common finding. Thinning or irregular lamina dura was observed in 1 child.”
SOURCE: Teotia M, Teotia SPS, Kunwar KB. (1971). Endemic skeletal fluorosis. Archives of Disease in Childhood 46: 686-691.
“Three major effects of fluoride on bone were found: (1) an increase in periosteal matrix and bone formation, (2) an inhibition of the process of mineralization at the periosteum, and (3) an increase in endosteal bone resorption… In terms of percent change from control values, fluoride increased periosteal formation much less than endosteal resorption; however, formation is an order of magnitude greater than resorption in the diaphysis of a growing rat. Consequently, a relatively small change in formation will have a substantial effect on the net amount of bone accumulated per day. Accordingly, fluoride increased bone area as well as total area and medullary area.”
SOURCE: Baylink D, et al. (1970). Effects of fluoride on bone formation, mineralization, and resorption in the rat. In: TL Vischer, ed. (1970). Fluoride in Medicine. Hans Huber, Bern. pp. 37-69.
“As the level of dietary fluoride intake increased, the mineral content of both the molar teeth and mandible decreased. The trend was statistically significant at the 2 1/2% level. The two lower fluoride conditions caused a loss of about 9% in mineral density; the 2 higher fluoride levels resulted in a loss of approximately 28% in density, when compared with the bone density in the control dogs which had not revealed fluoride supplementation.”
SOURCE: Henrikson PA, et al. (1970). Fluoride and nutritional osteoporosis. Fluoride 3: 204-207.
“Microradiographs in the fluorotic animals showed a marked increase in the number of the Haversian canals, disseminated patchy demineralization, irregular distribution of the lacunae and periosteocytal resorption of mineral salts.”
SOURCE: Freitag V, et al. (1970). Fluoride content and microradiograph findings in skeletal fluorosis. Fluoride 3: 167-174.
“There were enough signs of increased resorption in all the F treated animals to make it possible to distinguish them from the controls by viewing anonymous slides.”
SOURCE: Ramberg CF, Olsson SE. (1970). Fluoride effects on bone morphology and calcium kinetics. Fluoride 3: 175-181.
“The frequent description in the literature of large resorption cavities with fibrous tissue replacement suggested to me that the parathryoids were overactive in skeletal fluorosis, and this was demonstrated by an electron-microscopic study of the parathyroid glands from fluorotic sheep and a concomitant immunoassay of the amount of circulating parathyroid hormone, which was found to be as much as five times higher than resting levels and control levels.”
SOURCE: Faccini JM. (1969). Fluoride and bone. Calcified Tissue Research 3:1-16.
“Our findings indicate that osteocyte resorption was accentuated in both young and old bone. Increased osteocyte resorption has been observed in osteofluorosis, primary and secondary hyperparathyroidism, and in a number of conditions which result in cell injury.”
SOURCE: Baylink DJ, Bernstein DS. (1967). The effects of fluoride therapy on metabolic bone disease. Clinical Orthopaedics and Related Research 55: 51-85.
“Persistent high fluoride ingestion has been reported to produce a stimulation of osteoblastic activity, usually accompanied by an increased rate of bone resorption.”
SOURCE: Cohen MB, Rubini ME. (1965). The treatment of osteoporosis with sodium fluoride. Clinical Orthopaedics 40: 147-152.
“At high dosages (1 mg F/day) osteosclerosis is seen within a year; later, resorption cavities occur. At more moderate dosages (0.3 mg F/day) no osteosclerosis is seen but resorption cavities sometimes occur, however… The resorption cavities which occur in the animals show a micro-radiographic picture which would be expected from increased osteoclastic activity. These pictures have a distinct resemblance to the microradiograms of bone following radium radiation…”
SOURCE: Rockert H. (1963). X-ray absorption and x-ray fluorescence micro-analysis of mineralized tissue of rats which have ingested fluoridated water. Acta Pathologica et Microbiologica Scandinavica 59: 32-38.
“These considerations are in agreement with the statement of Weinman aned Sicher (1947), based on histologic evidence, that the fluorotic changes in bones, especially in young animals can be explained by an increased rate of resorption… It is suggested that the fluorine intake caused an increased rate of bone resorption in the primary and secondary spongiosa.”
SOURCE: Comar CL, et al. (1953). Effects of fluorine on calcium metabolism and bone growth in pigs. American Journal of Anatomy 92: 361-362.