Fluoride & Osteocytes

1) Fluoride's Impact on Osteocytes
2) Mechanism by which Fluoride May Damage Osteocytes
3) Osteocytes: Maintaining the Structural Health of Bone

1) Fluoride's Impacts on Osteocytes: (back to top)

"The increased amount of trabecular bone in fluoride therapy is claimed to be the morphologic expression for fluoride as a stimulus for bone formation. We propose that the increased amount of trabecular bone results from pathological bone formation by injured osteoblasts and decreased bone resorption by resorbing osteocytes and osteoclasts."
SOURCE: Krook L, Minor RR. (1998). Fluoride and alkaline phosphatase. Fluoride 31: 177-182.

"Some osteocyte lacunae in this zone were larger, more rounded, and irregularly arranged."
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.

"osteoblasts that survive as osteocytes are visibly abnormal."
SOURCE: Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393.

"Also noted were focal irregular arrangement of the osteocytes in 90% of the therapy group."
SOURCE: Vigorita VJ, Suda MK. (1983). The microscopic morphology of fluoride-induced bone. Clinical Orthopaedics and Related Research 177:274-282.

"The characteristics of (fluorotic) bone suggest an active, but irregular, metabolic process. Osteocytic cellularity, although significantly present in this group, may occur in a number of pathologic conditions, including most hypermetabolic areas, e.g. Paget's disease and hyperparathyroidism. These conditions may also show an irregular spatial distribution of osteocytes, a change found to a statistically significant degree in the (fluoride) therapy group, providing further evidence of an abnormal metabolic state."
SOURCE: Vigorita VJ, Suda MK. (1983). The microscopic morphology of fluoride-induced bone. Clinical Orthopaedics and Related Research 177:274-282.

"The primary target of fluoride was shown to be the resorbing osteocyte."
SOURCE: Krook L, Maylin GA. (1979). Industrial fluoride pollution. Chronic fluoride poisoning in Cornwall Island cattle. Cornell Veterinarian 69(Suppl 8): 1-70.

"The toxic effect of fluoride on the osteocytes then could go one step further to cause necrosis of the cells. Sometimes only empty lacunae were observed but with the architecture of bone still recognizable."
SOURCE: Krook L, Maylin GA. (1979). Industrial fluoride pollution. Chronic fluoride poisoning in Cornwall Island cattle. Cornell Veterinarian 69(Suppl 8): 1-70.

"Marked alterations in the fine structure of osteocytes are produced under the influence of the F diet. Large distensions of the endoplasmic reticulum and distorsions of ribosomal patterns are observed in the electron micrographs. These changes could influence the quality of the organic perilacunar matrix and its mineralization, and explain the presence of the uncalcified or poorly calcified perilacunar 'halo' also observed in the electron micrographs."
SOURCE: Baud CA, Bang S. (1970). Fluoride and bone mineral substance. In: TL Vischer, ed. (1970). Fluoride in Medicine. Hans Huber, Bern. pp. 27-36.

"The osteons show the irregularly distributed mineral salts and irregularly arranged osteocytes which tend to accumulate at the periphery of the osteon."
SOURCE: Freitag V, et al. (1970). Fluoride content and microradiograph findings in skeletal fluorosis. Fluoride 3: 167-174.

"Mineralization was particularly deficient around the osteocyte lacunae as visualized by the porosity picture."
SOURCE: Kuhlencordt F, et al. (1970). The histological evaluation of bone in fluoride treated osteoorosis. In: TL Vischer, ed. (1970). Fluoride in Medicine. Hans Huber, Bern.pp. 169-174.

"The osteocyte lacunae were larger than normal and in some areas these large lacunae were confluent."
SOURCE: Ramberg CF, Olsson SE. (1970). Fluoride effects on bone morphology and calcium kinetics. Fluoride 3: 175-181.

"The lack of mineralization around osteocyte lacunae was also evident in all samples..."
Jowsey J, et al. (1968). Some results of the effect of fluoride on bone tissue in osteoporosis. Journal of Clinical Endocrinology 28:869-874.

"The process of mineralization at the mineralizing front probably requires normally functioning osteoblasts and osteocytes. Degenerating osteocytes were found occasionally in the peripheral portion of wide osteoid seams and also in the adjacent mineralizing front. In addition, the lacunae and the canaliculi of osteoid osteocytes were sometimes larger than those in nonfluorotic bone. Thus, diminished or altered osteocyte function in this region may have also contributed to a decreased mineralization rate."
SOURCE: Baylink DJ, Bernstein DS. (1967). The effects of fluoride therapy on metabolic bone disease. Clinical Orthopaedics and Related Research 55: 51-85.

"An increased number of microfractures was frequently found in fluorotic bone. In nonfluorotic and fluorotic bone, microfractures were usually located in highly mineralized areas of old bone with an increased number of dead osteocytes... [D]ead and degenerating osteocytes were found frequently in the region of microfractures, and viable osteocytes appear to be necessary for the optimum mechanical function of bone. It is possible that osteocytes are involved in the maintenance of structural integrity at an ultra-microscopic level and that impaired osteocyte function increases the tendency for small defects to become microfractures."
SOURCE: Baylink DJ, Bernstein DS. (1967). The effects of fluoride therapy on metabolic bone disease. Clinical Orthopaedics and Related Research 55: 51-85.

2) Mechanism by which fluoride may damage Osteocytes (Bone F Accumulation): (back to top)

"[B]one cells would not be exposed to high concentrations (of fluoride) when they [a]re not resorbing bone. However, it is evident that any cells which resorb bone necessarily would be thereby exposed to a significant concentration of fluoride. This specific exposure would hold for osteocytes and osteoclasts throughout bone, both of which would be subjected to a concentration of fluoride which would be approximately proportionate to the intensity of the resorptive process. It could be speculated that the exposure of osteocytes, which are entirely surrounded by a surface on which fluoride probably is concentrated and which exist farther away from the blood stream, would be subjected to a higher concentration of fluoride upon resorbing bone than would be the osteoclasts. What fluoride does to these cells is unknown. We believe the action on bone cells would be a toxic one and that the consequence of a high regional concentration of fluoride would be inhibition of the resorptive function. There is ample evidence that fluoride passes into cells and that it inhibits numerous enzyme activities and therefore, the concept that metabolic function might be inhibited when cells are exposed to high fluoride concentrations is reasonable."
SOURCE: Rich C, Feist E. (1970). The action of fluoride on bone. pp. 70-87. In: Vischer TL. (1970). Fluoride in Medicine. Hans Huber, Bern.

3) Osteocytes: Maintaining the Structural Health of Bone (back to top)

"The results support the sensory role of the osteocyte network as the decline in osteocyte lacunar density in human cortical bone is associated with the accumulation of microcracks and increase in porosity with age. Porosity and microcrack density increased exponentially with a decline in osteocyte lacunar density indicating that a certain minimum number of osteocytes is essential for an “operational” network."
SOURCE: Vashishth D, et al. (2000). Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age. Bone 26:375-80.

"The impact of losing osteocytes in bone may be great. In human bone, osteocyte cell death can occur in association with age and both osteoporosis and osteoarthritis, leading to increased fragility. Such fragility may be due to increased brittleness via micropetrosis and/or loss of the ability to sense fatigue microfracture and signal to other cell types for repair."
SOURCE: Noble BS, et al. (1997). Identification of apoptotic changes in osteocytes in normal and pathological human bone. Bone 20:273-82.

"The co-localization of microfractures and osteocytes fits with the hypothesis that in vivo fatigue damage could be repaired by remodeling processes triggered by osteocytes."
SOURCE: Muglia MA, Marotti G. (1996). Osteocyte and microfracture location in human lamellar bone. Bone 19: 155S.

"We believe these experiments support the hypothesis that osteocytes are critical to regulation of bone formation and resorption. In contrast to osteoblasts or osteoclasts that must be signaled to appear, the omnipresent osteocytes are continually subject to the strain of the matrix and its derivatives such as strain-generated potentials and shear-induced fluid flow. These cells not only perceive and respond to local biophysical signals, they must also be responsive to a vast array of systemic chemical/hormonal signals of formation and resorption. Somehow these regulatory signals are perceived by the osteocyte population, and a message of maintenance, resorption, or formation is produced to retain a structurally adequate and metabolically efficient skeleton."
SOURCE: Sun YQ, et al. (1995). Mechanically induced periosteal bone formation is paralleled by the upregulation of collagen type one mRNA in osteocytes as measured by in situ reverse transcript-polymerase chain reaction. Calcified Tissue International 57:456-62.

"[D]ead and degenerating osteocytes were found frequently in the region of microfractures, and viable osteocytes appear to be necessary for the optimum mechanical function of bone. It is possible that osteocytes are involved in the maintenance of structural integrity at an ultra-microscopic level and that impaired osteocyte function increases the tendency for small defects to become microfractures."
SOURCE: Baylink DJ, Bernstein DS. (1967). The effects of fluoride therapy on metabolic bone disease. Clinical Orthopaedics and Related Research 55: 51-85.