Key Findings - Fluoride & Osteoid:

1) One of fluoride's most well-defined effects on bone tissue is it's ability to increase the osteoid (unmineralized bone) content of bone. This has been demonstrated in human clinical trials; in dialysis patients using dialysis systems which do not filter out fluoride from water; in animals exposed to high levels of fluoride; and in humans suffering from skeletal fluorosis.

2) Fluoride can increase osteoid volume to such an extent as to produce osteomalacia, a bone-softening disease marked by an excess amount of osteoid. This has been demonstrated in human clinical trials; in dialysis patients using dialysis systems which do not filter out fluoride from water; in animals exposed to high levels of fluoride; and in humans suffering from skeletal fluorosis.

3) Fluoride has been found to increase osteoid content in people (with normal kidney function) drinking water with only 1.5 ppm (Arnala 1985), and in people with impaired kidney function drinking water with 1 ppm (Ng 2004).

Definition - Osteoid:

"immature bone that has not yet undergone calcification."
SOURCE: Amersham Health

"Non-mineralised bone matrix."
SOURCE: International League of Associations for Rheumatology

"The protein product which becomes mineralized with calcium to form hard bones."
SOURCE: International Myeloma Foundation

Lowest Observed Effects - Fluoride & Osteoid:

"Increase in bone fluoride was associated with increased osteoid parameters and decreased bone microhardness... Fluoride interfered with bone mineralization and increased osteoid content, which was most evident in osteomalacia and the mixed bone disorder. In addition, fluoride may interact with aluminum to worsen the osteomalacic lesion."
SOURCE: Ng AHM, et al. (2004). Association between fluoride, magnesium, aluminum and bone quality in renal osteodystrophy. Bone 34: 216-224.

"The main histolological change induced by fluoride is the increase of osteoid volume... This increase in osteoid parameters was observed in our study already at fluoride concentrations above 1.5 ppm."
SOURCE: Arnala I, et al. (1985). Effects of fluoride on bone in Finland. Histomorphometry of cadaver bone from low and high fluoride areas. Acta Orthopaedica Scandinavica 56(2):161-6.

Human Clinical Trials - Fluoride & Osteoid: (back to top)

"Fluoride treatment increased all osteoid values significantlly when compared with the placebo control group."
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.

"Histomorphometry revealed a bulky trabeculare architecture, high osteoblastic activity and an increased amount of osteoid... "
SOURCE: Roschger P, et al. (1995). Bone mineral structure after six years fluoride treatment investigated by backscattered electron imaging (BSEI) and small angle x-ray scattering (SAXS): a case report. Bone 16:407.

"Evidence for a fluoride effect was present in seven of eight biopsies which were performed in patients on NaF, which could be evaluated qualitatively and quantitatively. This evidence consisted of a mineralization defect in all seven, increased osteiod (forming) surfaces and volume in six with (3 cases) evidence of increased osteoid thickness."
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.

"osteoid thickness was slightly but not significantly increased. Only two patients had thick osteoid seams suggesting the presence of osteomalacia."
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.

"the thickness of osteoid seams was slightly increased, the mineralization lag time was prolonged from 13 to 24 days, and the duration of formation increased from 78 to 110 days."
SOURCE: Kragstrup J, et al. (1989). Effects of sodium fluoride, vitamin D, and calcium on cortical bone remodeling in osteoporotic patients. Calcified Tissue International 45:337-41.

"When fluoride is given, especially at a high dosage without calcium, osteomalacia may develop. The newly formed matrix may be abnormal and may not undergo adequate mineralization. Thus, a typical histomorphometric picture is represented by a pronounced increase in osteoid (nonmineralized matrix) and reduced calcification front."
SOURCE: Pak CY. (1989). Fluoride and osteoporosis. Proceedings of the Society for Experimental Biology and Medicine 191: 278-86.

"Unfortunately, fluoride-induced osteoid, although plentiful, mineralizes slowly..."
SOURCE: Schnitzler CM, Solomon L. (1985). Trabecular stress fractures during fluoride therapy for osteoporosis. Skeletal Radioliology 14(4):276-9.

"histomorphometric analysis of a transilica bone biopsy specimen indicated an accumulation of osteid tissue due to impairment of mineralisation."
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.

"Fluoride stimulates osteoid production yet impairs its subsequent mineralization... Impaired bone mineralization producing thick osteoid seams has been a consistent histomorphometric finding in patients treated with sodium fluoride alone... The mineralization defect is less marked, and indeed, is sometimes absent when calcium supplements, with or without vitamin D, are given to patients treated with moderate doses."
SOURCE: Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393.

"An additional finding not observed in the control group was the presence in eight of ten fluoride cases of small foci of unmineralized bone or osteoid within trabecular and cortical mineralized bone. The authors termed these areas 'osteoid lakes.'"
SOURCE: Vigorita VJ, Suda MK. (1983). The microscopic morphology of fluoride-induced bone. Clinical Orthopaedics and Related Research 177:274-282.

"Morphologic studies of bone biopsy samples have shown that the predominant effect of fluoride therapy on the skeleton is osteoblastic stimulation. The newly formed osteoid tissue is poorly mineralized, resulting in the histologic picture of osteomalacia."
SOURCE: Jowsey J, et al. (1972). Effect of combined therapy with sodium fluoride, vitamin D and calcium in osteoporosis. American Journal of Medicine 53: 43-49.

"Following therapy with NaF, all cases demonstrated a widening of the osteoid seams, although to a variable extent."
SOURCE: Kuhlencordt F, et al. (1970). The histological evaluation of bone in fluoride treated osteoporosis. In: TL Vischer, ed. (1970). Fluoride in Medicine. Hans Huber, Bern. pp. 169-174.

"a retardation of osteoid mineralization became obvious, showing its maximum after 40 weeks of treatment."
SOURCE: Reutter FW, et al. (1970). Fluoride in osteoporosis: clinical and quantitative histological studies on bone structure and bone remodelling. Fluoride 3: 209.

"The bone tissue (formed in fluoride therapy ) was most abnormal; large areas consisted entirely of incompletely calcified bone with large, irregular lacunae surrounded by areas of low mineral density."
SOURCE: Jowsey J, et al. (1968). Some results of the effect of fluoride on bone tissue in osteoporosis. Journal of Clinical Endocrinology 28:869-874.

"Sodium fluoride, 100 mg (= 45 mg fluoride ion) daily for 14 months, was administered to a patient with osteoporosis associated with continuing corticosteroid therapy. New bone formation and fluoride incorporation in bone was demonstrated. After eight months, much of this new bone appeared to be in the form of uncalcified osteoid material."
SOURCE: Cass RM, et al. (1966). New bone formation in osteoporosis following treatment with sodium fluoride. Archives of Internal Medicine 118: 111-116.

Patients with Kidney Disease using Dialysis with Fluoridated (1 ppm) water: Fluoride & Osteomalacia: (back to top)

NOTE: For more detailed information on fluoridation & diaylsis, click here

"In the fluoridated group, osteoid seams were more abundant and wider than in the non-fluoridated group... This study has shown that hemodialysis with fluoridated water in chronic renal failure induces the activated osteoblasts to produce excessive osteoid in which the collagen fibrils are disarrayed. The risk of severe osteomalacia is reduced with the use of fluoride-free dialysate."
SOURCE: Lough J, et al. (1975). Effects of fluoride on bone in chronic renal failure. Archives of Pathology 99: 484-487.

"There was a marked increase in the amount of osteoid tissue on bone biopsy in the fluoridated group."
SOURCE: Cordy PE, et al. (1974). Bone disease in hemodialysis patients with particular reference to the effect of fluoride. Transactions of the American Society of Artifical Internal Organs 20: 197-202.

"All 4 patients exposed to high-fluoride dialysate showed excessive osteoid formation... osteoid formation was 9 times greater in those exposed to high-fluoride dialysate (1 ppm) than in those exposed to lower concentrations (0.095 ppm)... The presence of increased amounts of osteoid tissue in patients exposed to high-F dialysate is consistent with the observations of DeVeber and associates... Increased osteoid is typically found in fluorosis, hence, ascribing our findings to an F effect seems reasonable. There are several possible reasons for F causing increased osteoid. In vivo, excessive F can result in increased bone production and failure of mineralization."
SOURCE: Jowsey J, et al. (1972). Effects of dialysate calcium and fluoride on bone disease during regular hemodialysis. Journal of Laboratory and Clinical Medicine 79: 204-214.

"we found that we could not only prevent symptomatic osteomalacia by deionization, but could also reverse its course. This suggests that there was a factor in our tap water which prevented normal calcification of osteoid and that this is removed by deionization. We have previously reported high uptake of fluoride with an increase in the serum and bone levels of fluoride in our patients dialyzed with ordinary tap water. DeVeber and Jowsey have observed an increase in osteoid similar to ours in their dialysis patients treated with high fluoride dialysate. High fluoride concentrations have also been shown experimentally to lead to a defect in osteoid calcification. These observations suggest a role for fluoride in the osteomalacic disease in dialysis patients."
SOURCE: Posen GA, et al. (1972). Comparison of renal osteodystrophy in patients dialyzed with deionized and non-deionized water. Transactions of the American Society for Artificial Internal Organs 18: 405-411.

Animal Studies - Fluoride & Osteoid: (back to top)

"In contrast to calcium phosphate deficiency, high fluoride intake had no effect on trabecular bone volume, but instead increased the amount of unmineralized osteoid, particularly in older rats. This impairment of mineralization by fluoride appeared to be the primary cause of the diminshed vertebral strength."
SOURCE: Turner CH, et al. (2001). Combined effects of diets with reduced calcium and phosphate and increased fluoride intake on vertebral bone strength and histology in rats. Calcified Tissue International 69: 51-57.

"[O]steoid volume was increased over 20-fold in animals with renal deficiency that received 15 or 50 ppm fluoride. Increases in osteoid can result from either increased osteoid formation or impaired mineralization... The osteoid, which contributed to the bone volume, did not contribute to the bone strength."
SOURCE: Turner CH, et al. (1996). High fluoride intake causes osteomalacia and diminished bone strength in rats with renal deficiency. Bone 19: 595-601.

"osteoid surface was significantly higher in the NaF groups by 48-75%... osteoid thickness was modestly increased (by 12%) in the NaF group..."
SOURCE: Lafage MH, et al. (1995). Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs: a one year study. Journal of Clinical Investigations 95: 2127-2133.

"fluoride-treated, aluminum-loaded rats accumulated a sevenfold larger amount of osteoid volume as compared to (the aluminum-only group) and exhibited an increase in osteoid surface of a corresponding degree. As a consequence of the severe osteoidosis, cancellous bone volume almost doubled in rats exposed to fluoride and aluminum."
SOURCE: Ittel TH, et al. (1992). Effect of fluoride on aluminum-induced bone disease in rats with renal failure. Kidney International 41: 1340-1348.

"It is possible that deposition of aluminum-fluoride complexes at the mineralized bone-osteoid interface disturb mineralization more effectively than aluminum itself."
SOURCE: Ittel TH, et al. (1992). Effect of fluoride on aluminum-induced bone disease in rats with renal failure. Kidney International 41: 1340-1348.

"Results of this study indicated that the ingestion of fluoride produced wide osteoid seams on the periosteal surface of the femoral diaphysis within 4 weeks. The increase in osteoid appeared to be due to an increase in the number of osteoid-producing cells (osteoblasts) along with a subsequent delay in the mineralization of this tissue."
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.

"The effect of fluoride on bone appears to be one of increased turnover with matrix formation exceeding resorption. Mineralization of newly-formed matrix is imperfect and much of the bone appears as woven or immature bone with components of unmineralized matrix resembling osteomalacia."
SOURCE: Riggins RS, et al. (1974). The effects of sodium fluoride on bone breaking strength. Calcified Tissue Research 14: 283-289.

"Periosteal osteoid width was significantly more in rats treated with 100 ppm fluoride in the drinking water than in controls in experiment 1 and also in experiment 2. The increase in periosteal osteoid width was sufficiently more than the increase in periosteal matrix apposition in both experiments 1 and 2 so as to result in a prolongation of the mineralization lag time (i.e. an increase in the time between osteoid formation and the onset of mineralization)."
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.

"By using a battery of special stains, as well as polarized, infrared, and ultraviolet light, it could be demonstrated that the changes of the collagen matrix, which normally precede calcification, had not developed, and that the osteoid was in fact uncalcifiable."
SOURCE: Johnson LC. (1965). Histogenesis and mechanisms in the development of osteofluorosis. In: H.C.Hodge and F.A.Smith, eds : Fluorine chemistry, Vol. 4. New York, N.Y., Academic press 424-441.

"the sections from the treated animals show definite evidence of an increasing osteoid border with the higher fluorine. It thus appears that there was matrix present in bones from the fluorine animals; the fact that this matrix was devoid of calcium may mean that the osteoid produced was not capable of holding bone salts or that there was a disturbance in the system by which the bone salts were deposited."
SOURCE: Comar CL, et al. (1953). Effects of fluorine on calcium metabolism and bone growth in pigs. American Journal of Anatomy 92: 361-362.

Skeletal Fluorosis - Fluoride & Osteoid: (back to top)

In the fluorosis patients "histopathological assessment of the undecalcified sections of iliac crest biopsies showed loops and bridges of wide osteoid seams (> 50 u)..."
SOURCE: Teotia M, Teotia SP, Singh KP. (1998). Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone disease and deformities in India: year 2000. Indian Journal of Pediatrics 65:371-81.

"In fluorosis one observes mineralization defects (areas of unmineralized osteiod) existing with highly mineralized areas ['mottled bone']."
SOURCE: Fratzl P, et al. (1994). Abnormal bone mineralization after fluoride treatment in osteoporosis: a small-angle x-ray-scattering study. Journal of Bone and Mineral Research 9:1541-9.

"Cancellous osteoid volume and perimeter, as well as width of osteoid seams, were significantly increased in fluorotic patients... Eight patients showed a true histological osteomalacia with both a significantly increased osteoid width and a significantly decreased mineral apposition rate... Thus the hyperosteoidosis frequently noted in skeletal fluorosis was confirmed."
SOURCE: Boivin G, et al. (1989). Skeletal fluorosis: histomorphometric analysis of bone changes and bone fluoride content in 29 patients. Bone 10:89-99.

"The bone biopsy (of the fluorosis patient) was remarkable for increased osteoid and mineralized bone and was interpreted as quiescent Paget's disease or another nonneoplastic sclerotic disease."
SOURCE: Fisher RL, et al. (1989). Endemic fluorosis with spinal cord compression. A case report and review. Archives of Internal Medicine 149: 697-700.

"Fluoride stimulates osteoid production yet impairs its subsequent mineralization... Impaired bone mineralization producing thick osteoid seams has been a consistent histomorphometric finding in patients treated with sodium fluoride alone... The mineralization defect is less marked, and indeed, is sometimes absent when calcium supplements, with or without vitamin D, are given to patients treated with moderate doses."
SOURCE: Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393.

"Thickening of the osteoid seams was the most striking and most consistent feature.Cancellous bone was mainly involved. It was rarely observed in cortical bone."
SOURCE: Pinet A, Pinet F. (1968). Endemic fluorosis in the Sahara. Fluoride 1: 85-93.

"So-called 'osteoid-seams' were prominent in places."
SOURCE: Webb-Peploe MM, Bradley WG. (1966). Endemic fluorosis with neurological complications in a Hampshire man. Journal of Neurology, Neurosurgery and Psychiatry 29:577-583.

"In the spongy bone, areas of osteoid tissue were found among well-formed trabeculae. Some of the irregular deposits of osteoid tissue extended into the attached muscle."
SOURCE: Singh A, et al. (1963). Endemic fluorosis. Epidemiological, clinical and biochemical study of chronic fluoride intoxication in Punjab. Medicine 42: 229-246.

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