Key Findings - Fluoride's Differential Effect on Bone Density:

Fluoride's impact on bone density differs depending on the type of bone. While fluoride tends to increase the density of trabecular bone (aka cancellous bone), it tends to decrease the density of cortical bone.

Fluoride's differential effect on bone density has been observed in human clinical trials, studies on individuals with skeletal fluorosis, and studies comparing bone density in high-fluoride versus low-fluoride areas.

Since trabecular bone is the primary bone of the axial skeleton (spine, pelvis, and ribs), fluoride has a greater tendency towards increasing bone density in these areas than it does in the appendicular skeleton (legs, arms, hip) where the primary bone type is cortical.

As is now widely acknowledged, fluoride-induced increases in bone density are not accompanied by corresponding increases in bone strength. Fluoride-induced decreases in bone density, however, would be expected to decrease bone strength, which may explain the increased incidence of hip fracture in human clinical trials and in populations drinking fluoridated water over the course of a lifetime.

Human Clinical Trials - Fluoride's Differential Effect on Bone Density: (back to top)

"The BMD changes in the present study are suggestive of an anabolic action of fluoride at trabecular sites (the spine) and a catabolic action at cortical sites (the femoral neck)."
SOURCE: Morabito N, et al. (2003). Three-year effectiveness of intravenous pamidronate versus pamidronate plus slow-release sodium fluoride for postmenopausal osteoporosis. Osteoporosis International 14: 500-6.

"significant bone loss occurred by 27 months at all nonspinal sites examined. The greatest loss occurred in the lower tibia/fibula, where the loss at the shaft site was 7.3%. The lower tibia/fibula is a common site of fluoride-related stress fractures and these BMD results help to explain the mechanism of this common complication of treatment with NaF."
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(2):158-70.

"Forearm bone density was actually lower in the fluoride groups at both 2 and 4 years. Since the forearm has a different composition of trabecular and cortical tissue, this differential effect might be expected."
SOURCE: Haguenauer D, et al. (2000). Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis. Osteoporosis International 11:727-38.

"It is a consistent finding that fluoride treatment in osteoporosis results in greater amounts of trabecular bone and a decrease in cortical bone."
SOURCE: Krook L, Minor RR. (1998). Fluoride and alkaline phosphatase. Fluoride 31: 177-182.

"It is important to note that Femoral Neck BMD in some individuals decreased markedly (by as much as 19%) for a minimal increment in Lumbar Spine. This does suggest that fluoride therapy can decrease Femoral Neck BMD (and possibly increase fracture risk) without any potential benefit at the lumbar spine... [A]ll patients treated with fluoride need to have BMD measurements at the Lumbar Spine and Femoral Neck to allow discontinuation of fluoride if this disparity in BMD changes is observed."
SOURCE: Patel S, et al. (1996). Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density. Bone 19:651-5.

"Fluoride has been shown to increase bone formation to a larger extent in trabecular bone than cortical bone and, therefore, to exert a greater response in the axial than the appendicular skeleton."
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.

"The osteogenic effect has consistently been documented in trabecular bone of the axial skeleton. The effect of fluoride on the peripheral skeleton is less clear and experience has been primarily limited to the radius, where bone density was either reduced or unchanged during fluoride therapy."
SOURCE: Dure-Smith BA, et al. (1991). Fluoride therapy for osteoporosis: A review of dose response, duration of treatment, and skeletal sites of action. Calcified Tissue International 49(Suppl): S64-S67.

"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.

"Because of the association between hip fracture and low femoral cortical thickness, and because of the reported decrease in cortical forearm density using Ca and NaF, it seems unwise to use NaF treatment in patients with hip fracture following minor trauma."
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 the lumbar spine, a site containing a predominance of cancellous bone, the bone mineral density increased linearly at a rate of about 10 percent per year. In contrast, there was a substantial loss of bone from the shaft of the radius, a site with a predominance of cortical bone. Decreases in bone mineral content in the radial shaft have been found previously during fluoride treatment. Ruegsegger used computed tomography to assess the changes in the two types of bone and found a gain in cancellous bone but a loss in cortical bone. These results suggest that fluoride therapy causes a redistribution of bone from the cortical to the cancellous department."
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.

"It has been shown that fluoride therapy can actually increase lumbar spine density and increase trabecular bone volume on iliac crest biopsies. The effect of therapeutic doses of fluoride on cortical bone, however, is not as clear. Bone mass measured at sites of predominantly cortical bone showed either no change or small decreases after fluoride therapy. These findings led Eastell and Riggs (1987) to state that 'Some evidence suggests that trabecular bone may increase at the expense of cortical bone during fluoride therapy.'"
SOURCE: Phipps KR, Burt BA. (1990). Water-borne fluoride and cortical bone mass: a comparison of two communities. Journal of Dental Research 69: 1256-1260.

"We have documented a clinically relevant increase in vertebral BMD, although there was a significant reduction in cortical BMD at the radial site... In the absence of a control group it is not possible to conclude from our data whether a significant response to fluoride in trabecular or axial skeletal sites necessarily translates into higher than expected losses from cortical bone. This is of some concern, because fluoride therapy has been implicated as a cause of increased frequency of femoral neck fractures, as occurred in 2 of our patients... Although data on femoral neck BMD were not available in this study, clearly such measurements would have been of great importance."
SOURCE: Hodsman AB, Drost DJ. (1989). The response of vertebral bone mineral density during the treatment of osteoporosis with sodium fluoride. Journal of Clinical Endocrinology and Metabolism 69:932-8.

"The site of predilection for stress fractures, namely the metaphysis, with its thin cortex, may be determined by the decrease in cortical bone mass observed in fluoride therapy."
SOURCE: Schnitzler CM, Solomon L. (1985). Trabecular stress fractures during fluoride therapy for osteoporosis. Skeletal Radioliology 14(4):276-9.

"The dramatic increase in the predominantly trabecular bone of the axial skeleton during fluoride therapy is not accompanied by a corresponding increase in the predominantly cortical bone of the appendicular skeleton... Indeed, several investigators have reported that cortical bone decreases significantly during treatment...These reports raise the possibility that fluoride therapy may protect against fractures of the vertebral bodies (which consist of predominantly trabecular bone) but may not protect the proximal femur, and could even increase the risk for fractures of this bone, which is predominantly cortical...Since hip fracture is more catastrophic than is vertebral fracture, it will be important for future studies to evaluate the effect of sodium fluoride therapy on mineral content of the proximal femur."
SOURCE: Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: an appraisal. Bone and Mineral Research. 2: 366-393.

"In this series, we found increased vertebral trabeculation in one third of the patients, but this was associated with, if anything, decreased density of the distal radius, a site containing predominantly cortical bone. The possibility that trabecular (lamellar) bone is increased at the expense of cortical (osteonal) bone cannot be excluded at the present time."
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: 446-44.

Studies on Skeletal Fluorosis- Fluoride's Differential Effect on Bone Density: (back to top)

"In skeletal fluorosis, involvement of the axial skeleton is characteristic, and changes are most marked in the spine, pelvis, and forearm."
SOURCE: Savas S, et al. (2001). Endemic fluorosis in Turkish patients: relationship with knee osteoarthritis. Rheumatology International 21: 30-5.

"It is very interesting to observe that in the majority of our cases, osteosclerosis in the spine and pelvis was always combined with osteoporosis of the long bones. It might be an indication that the axial skeleton undergoes a quite different pathological process from the appendicular skeleton..."
SOURCE: Lian ZC, Wu EH. (1986). Osteoporosis--an early radiographic sign of endemic fluorosis. Skeletal Radiology 15:350-3.

"Osteosclerosis was particularly prominent in axial bones of the spine, pelvis, and ribs... The peculiarity of peripheral osteomalacia was its frequent association with axial osteosclerosis... Some cases showed axial osteosclerosis exclusively, others axial osteosclerosis in association with peripheral osteoporosis or osteomalacia."
SOURCE: Daijei H. (1984). Further observations on radiological changes of endemic foodborne skeletal fluorosis. Fluoride 17: 9-14.

"significantly higher values were obtained for trabecular bone volume (p<0.05), cortical porosity (P<0.005) and periosteocytic lacunar surface (p<0.0005) of fluorotic bone tissue as compared with the control samples."
SOURCE: Bang S, et al. (1978). Morphometric and biophysical study of bone tissue in industrial fluorosis. In: B Courvoisier, A Donath, CA Baud, eds. Fluoride and Bone. Hans Huber Publishers, Bern. pp. 168-175.

"In skeletal fluorosis, the spinal column is the site of election. Spinal osteosclerosis resulting from chronic fluoride intoxication may be expected to divert calcium preferentially to the spinal column at the expense of limb bones. In the presence of low dietary calcium such diversion may well result in osteoporosis of the limb bones."
SOURCE: Krishnamachari KA, Krishnaswamy K. (1973). Genu valgum and osteoporosis in an area of endemic fluorosis. The Lancet 2: 877-879.

"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.

"From the description here given it will be seen that in the severe cases all the bones are affected, but that the intensity of the changes becomes less from the centre outwards toward the periphery, being always most pronounced in the vertebral column and the pelvis. It is also in these portions of the skeleton that the first stages of the densification can be discovered..."
SOURCE: Moller P, Gudjonsson SV. (1932). Massive fluorosis of bones and ligaments. Acta Radiologica 12: 269-294.

Comparing High-Fluoride vs. Low-Fluoride Areas - Fluoride's Differential Effect on Bone Density: (back to top)

"Depending upon which fluoride exposure method is used, two different sets of conclusions can be drawn from this study. If the ecologic measure (city of residence) is used, then exposure to higher levels of fluoride in community water systems increases lumbar spine and proximal femur BMD. If the individual level measure (daily fluoride intake) is used, then exposure to higher levels of fluoride in community water systems decreases forearm BMD... The anatomical site differences noted in both the ecologic and individual level analyses may be partially explained by differences in the proportions of cortical vs trabecular bone at each site. Cortical bone accounts for 50 to 95% of the forearm, depending upon the region of interest, while only 10 to 33% of the vertebrae is cortical bone... The differential impact of fluoride on cortical and trabecular bone has been demonstrated in a recent clinical trial where fluoride was used as a therapy for osteoporosis."
SOURCE: Phipps KR, et al. (1998). The association between water-borne fluoride and bone mineral density in older adults. Journal of Dental Research 77:1739-1748.

"young women in the higher-fluoride community had significantly lower mean bone mass than did women in the control and higher-calcium communities. Furthermore, the mean loss of radial bone (primarily cortical), expressed as absolute difference or percentage of loss, was greater in women of the higher-fluoride community than in women of the control and higher-calcium communities... We could determine no reason, apart from the higher fluoride exposure, why women in the higher-fluoride community should have greater loss of bone mass than women in the other two communities."
SOURCE: Sowers MR, et al. (1991). A prospective study of bone mineral content and fracture in communities with differential fluoride exposure. American Journal of Epidemiology 133: 649-660.

"living in a community with high levels of water-borne fluoride was associated with decreased bone mass*... a Lordsburg woman (high-fluoride community, 3.5 ppm) had approximately 7% less bone mass than a Deming (low fluoride community) peer of similar weight and years since menopause... The negative association we found between fluoride exposure and bone mass was not an anticipated result, since this study was stimulated by the hypothesis that fluoride may actually prevent overall skeletal osteopenia by increasing cortical bone mass. However, we cannot attribute this result to bias or random error, since the other significant findings were consistent with theoretical considerations and prior research." (*"For this study, bone mass of the distal radius (75% cortical bone) was utilized as the measure of cortical bone osteopenia.")
SOURCE: Phipps KR, Burt BA. (1990). Water-borne fluoride and cortical bone mass: a comparison of two communities. Journal of Dental Research 69: 1256-1260.

"If therapeutic doses of fluoride do have a differential effect on cortical and trabecular bone mass (in clinical trials), a differential effect may also be noted at lower doses."
SOURCE: Phipps KR, Burt BA. (1990). Water-borne fluoride and cortical bone mass: a comparison of two communities. Journal of Dental Research 69: 1256-1260.

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