The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention

Osteoclasts were isolated mechanically from bones of prehatch chicks and cultured on dentine for 24 or 39 h in medium without or with added sodium fluoride at concentrations of 0.15, 1, 15, or 30 mg/liter. Fixed and toluidine blue-stained specimens were examined by light microscopy and osteoclasts were counted, all cells were removed and resorption pits were counted. The dentine was then prepared for scanning electron microscopy (SEM) and pits located on a raster search using backscattered electron imaging. Stereophotogrammetric measurements were made of the depths, plan and true surface areas and volumes of pits, and the volume:area ratio and a three-dimensional form factor calculated for each. The presence or absence of a ring of demineralization around each pit was recorded. Pits with the same plan area were significantly (p less than 0.001) less deep in cultures containing 15 or 30 mg/liter NaF and the incidence of rings around pits was higher (controls 2.7%, 15 mg/liter 31.3%, 30 mg/liter NaF 39.7%). In one experiment, pits were larger in the specimen cultured with added 1 mg/liter NaF, but in a much larger series of 631 (251 in the control and 380 in the 1 mg/liter NaF cultures) pits measured, depths, volumes and volume:plan-area ratios were significantly lower (p less than 0.001), and rings round pits 2.5 times more common, in the fluoride-treated group. A complex interplay of stimulation of some cells in the culture with indirect stimulation of osteoclasts and direct inhibition of osteoclastic resorptive function may be operating at this concentration of fluoride. In vivo, therapeutic doses of sodium fluoride would be expected to act not only to increase the formation of osteoid but also to suppress osteoclastic activity.

Section: Introductionmentioning

confidence: 99%

Journal of Bone and Mineral Research

Taylor

Maconnachie

Frank

et al. 1990

“…(12) Urine total hydroxyproline was measured by the method of Goverde and Veenkamp.P" 45Ca intestinal calcium absorption was determined as previously described. (7) Bone biopsy cores were taken from the posterior iliac crest at 0, 12, and 48 months of therapy using a Vilaghy bone biopsy needle (3 mm inner diameter) and morphometric analysis carried out as previously described.i" Hyperosteoidosis was considered to be present if osteoid volume (OVlTV) was greater than 5%14; we previously found that values greater than 5% correlate with accretion of bone mineral in fluoride-treated patients. (2) Bone fluoride was assessed on all bone biopsy cores nondestructively by neutron activation analysis, as described previously.v" Statistical Analysis.…”

Section: Patient Selection and Study Protocolmentioning

confidence: 99%

“…In 12 patients, calcium and vitamin D were discontinued; in 4 because of hypercalcemia, in 2 because of GI intolerance of the calcium supplement, and in 6 because of apparent poor fluoride absorption'I'; in 8 of the 13 patients with calcium discontinued without concomitant change in fluoride dose, serum fluoride increased significantly by a mean of 33% (from a mean of 5.2 to a mean of 6.9 umol/liter (p < 0.05), somewhat less than in our previous report. (7).1 The overall distribution of NaF doses received by the patients after correcting for alterations in dose is shown in Table 3. The mean dose (corrected for time on a given dose) for all patients was 44.2 mg/day; for the 45 patients who took the enteric-coated tablets for most of the study, the mean dose was 42.3 mg/day (19.1 mg elemental fluoride).…”

Section: Patient Selection and Study Protocolmentioning

confidence: 99%

Journal of Bone and Mineral Research

Murray

Harrison

Bayley

et al. 1990

Self Cite

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

“…However, not all treated patients show a beneficial effect. (7)(8)(9) Fluoride causes a dose-dependent change in the quality of bone with a delay in mineralization and transient hyperosteoidosis, an increased compression resistance and a decrease in torsion resistance. (4,1l>-12) It has been postulated that the molecular mechanism of the mitogenic action of fluoride is based on inhibition of osteoblastic acid phosphatase-like phosphotyrosyl protein phosphatase activity.…”

Section: Introductionmentioning

confidence: 99%

Journal of Bone and Mineral Research

Duursma

Raymakers

Raadt

et al. 1990

The aim of the study was to investigate the usefulness of urinary fluoride excretion in evaluating fluoride therapy. In a prospective study, 35 patients with osteoporosis were treated for about 44 months with a mean dosage of 31.4 mg fluoride ion per day. Urinary fluoride excretion and serum alkaline phosphatase activity were measured at 3-month intervals. Bone mineral content (BMC) was measured in L2-L4 with dual-photon absorptiometer. The mean number of BMC measurements was 5.7 per patient. The interindividual reproducibility for measurements in 10 patients was 2.1%. For each individual, the regression coefficient of BMC for the period of treatment was calculated. Responders were defined as those who had a positive value and nonresponders had 0 or a negative value. The percentage responders was 83%. Between responders and nonresponders no differences were found for age, fluoride dosage, duration of treatment, or changes in serum alkaline phosphatase activity. Urinary fluoride excretion was higher in responders than in nonresponders (p less than 0.001) and a positive correlation (p less than 0.001) was obtained between the changes in BMC and urinary fluoride excretion. In the responders, 90% had a urinary fluoride excretion greater than 8 mg/24 h. All nonresponders had a urinary fluoride excretion less than 8 mg/24 h. Urinary fluoride excretion is a valuable predictor of BMC response during fluoride therapy for osteoporosis.