Treatment of Postmenopausal Osteoporosis with Slow-Release Sodium Fluoride: Final Report of a Randomized Controlled Trial

Pak, Charles Y.C.; Sakhaee, Khashayar; Adams‐Huet, Beverley; Piziak, Veronica; Peterson, Roy D.; Poindexter, John R.

doi:10.7326/0003-4819-123-6-199509150-00001

Cited by 226 publications

(63 citation statements)

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“…In conclusion, our data suggest that if there is a therapeutic future for NaF in osteoporosis, it lies with earlier administration and with low-dose regimens in which toxic blood levels are avoided and mineralization is not impaired [3,25,43,44].…”

Section: Discussionmentioning

confidence: 98%

“…NaF could thicken, and possibly strengthen, horizontal trabeculae, but cannot replace them once they have been lost. This would account for the inconsistent effect of fluoride in reducing vertebral fracture frequency, despite its consistent effect in increasing vertebral bone mass [1,31], and for its greater efficacy in patients with less severe disease [3].…”

Section: Discussionmentioning

confidence: 98%

“…More recently, controlled trials of a lower dose of NaF have given the same outcome for bone density but conflicting outcomes for vertebral fractures [3,4]. Several explanations have been proposed for these seemingly paradoxical results.…”

Section: Introductionmentioning

confidence: 97%

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Effects of Different Regimens of Sodium Fluoride Treatment for Osteoporosis on the Structure, Remodeling and Mineralization of Bone

Balena

Kleerekoper

Foldes

et al. 1998

Osteoporosis International

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We compared initial and final bone histomorphometric findings in 66 osteoporotic patients treated with sodium fluoride (NaF) according to three regimens, and in 7 osteoporotic patients who did not receive NaF. Fourteen patients received continuous NaF 75 mg/day (high-dose) with calcium 1500 mg/day for a mean of 41 months. Twenty-six patients received continuous NaF 50 mg/day (low-dose) with calcium 2000 mg/day for a mean of 15 months, either with (10 patients) or without (16 patients) vitamin D. Twenty-six patients received cyclical low-dose NaF, alternating with vitamin D, for a mean of 15 months and a total treatment duration of 28 months, of whom 14 were and 12 were not on NaF at the time of the second biopsy. Disregarding differences between regimens, there were significant increases in total and mineralized bone volume and trabecular thickness and nonsignificant decreases in these measurements in the control group. Fluoride-induced bone formation was exclusively appositional with no evidence for the creation of new trabeculae. The effect of low-dose NaF on bone structure was the same when the same total dose was given continuously or intermittently, and when the patient was or was not taking vitamin D. The increases in total and mineralized bone volume but not trabecular thickness were greater with high-dose than with low-dose NaF. Low-dose NaF caused modest but significant increases in all osteoid indices, and modest but significant declines in adjusted apposition rate and osteoid maturation rate and no change in bone formation rate. With high-dose NaF, the increase in BV/TV was greater but all indices of osteoid accumulation were much higher and all indices of impaired osteoblast function and mineralization were much lower, and 12 of 14 patients had some form of osteomalacia. This occurred also in 3 of 30 patients treated with low-dose NaF who were not taking vitamin D; the mean increase in osteoid thickness was significantly greater in these patients than in 22 low-dose patients who were taking vitamin D. We conclude: (1) The inconsistent effect of NaF in increasing bone strength is partly due to failure to restore connectivity in patients with severe bone loss and partly due to substantial osteoid accumulation. (2) Even low-dose NaF causes impaired osteoblast function, but this is much greater with high-dose prolonged therapy. (3) There is an unexplained discrepancy between the increase in bone formation implied by increases in spinal bone mineral and the lack of increase in bone formation measured histomorphometrically. (4) Defective mineralization is more closely related to the total cumulative dose of NaF than to the duration of treatment, and with low-dose treatment may be preventable by vitamin D. (5) Future clinical trials should be carried out with smaller doses of NaF and before there has been substantial loss of horizontal trabeculae in the spine.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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Effects of Different Regimens of Sodium Fluoride Treatment for Osteoporosis on the Structure, Remodeling and Mineralization of Bone

Balena

Kleerekoper

Foldes

et al. 1998

Osteoporosis International

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“…To avoid these adverse effects, active research is currently in progress with slow-release sodium¯uoride for the treatment of osteoporosis, and preliminary results point to fracture reduction in trabecular bone [499,500] with increased bone formation markers [501]. However, slow-release sodium¯uoride therapy seems to have only a small, but statistically signi®cant effect on spinal fracture rates despite a marked augmentation of spinal bone mass [150,499,502,503].…”

Section: Sodium Fluoridementioning

confidence: 96%

Drug-Induced Bone Loss

Tannirandorn

Epstein

2000

Osteoporosis International

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Bone loss leading to osteoporosis is common after the menopause and in the elderly but uncommon in normal young adults without predisposing factors. The risk factors usually associated with osteoporosis include a family history of osteoporosis or fractures, aging, prior diseases, sedentary lifestyle, low calcium intake, hypogonadism, vitamin D deficiency, smoking, and excessive alcohol consumption. However, the issue of drugs has to be considered in 'normal' individuals who present with osteoporosis or bone loss without predisposing genetic or other environmental factors. The list of drugs is extensive and includes, amongst others, glucocorticoids, thyroid hormone (excess), alcohol, medroxyprogesterone acetate, luteinizing hormone-releasing hormone agonists, anti-seizure medications, cyclosporine A, aluminium, lithium, and exchange resins. This paper reviews the pathophysiology and mechanisms of drug-induced bone loss, which includes osteoporosis and osteomalacia, and treatment concepts. Undoubtedly, physician awareness, appropriate investigation, careful prescribing, monitoring, and proper therapy for this eminently preventable side effect can preserve bone in the patients receiving bone-losing drugs.

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“…Therefore, prediction of the bone fracture risks and treatment to increase the amount of bone mineral mass are essential. For patients suffering from osteoporosis, orthopedic surgeons usually prescribe a drug treatment to increase the bone mass (4)(5)(6) and vertebral strength. Clinically, the typical methods available for assessing the severity and recovery of bone mass in osteoporosis during drug treatment involve quantification of the bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA) (7,8) .…”

Section: Introductionmentioning

confidence: 99%

Patient-Specific Finite Element Analyses Detect Significant Mechanical Therapeutic Effects on Osteoporotic Vertebrae During a Three-Year Treatment

Tawara

Sakamoto

Murakami

et al. 2011

JBSE

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Analyses of the bone mass alone of osteoporotic vertebrae are not sufficient to predict fracture risks and assess the recovery of bone strength during drug treatment. Instead, finite element analyses (FEAs) is superior, because changes in the vertebral strength are strongly dependent on the inner vertebral stress distribution, which is related to the individual bone shape and bone density distribution in cancellous and cortical region. To investigate how FEAs can detect drug effects, we performed patient-specific FEAs of the first lumbar vertebra of osteoporotic patients at five time points (before therapy, and after 6 and 12 months and 2 and 3 years of therapy) during a 3-year drug treatment with alendronate and vitamin D, in four osteoporotic female patients in this study. The FEAs revealed notable decreases in the compressive principal strains in cancellous bone, but these decreases did not necessarily correspond to increases in the bone densities. In addition, statistical analyses by Friedman's test (nonparametric analysis) showed that evaluation based only on the average compressive principal strains over the 3-year treatment identified drug effects significantly, suggesting that compressive principal strain is an useful indicators for monitoring drug effects. Our data implied that compressive fracture of the vertebrae may be prevented as a result of the drug treatment, in a manner that was optimally detectable by patient-specific FEAs.

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Treatment of Postmenopausal Osteoporosis with Slow-Release Sodium Fluoride: Final Report of a Randomized Controlled Trial

Abstract: Slow-release sodium fluoride and calcium citrate administered for 4 years inhibits new vertebral fractures (but not recurrent fractures), augments spinal and femoral neck bone mass, and is safe to use.

Cited by 226 publications

References 0 publications

Effects of Different Regimens of Sodium Fluoride Treatment for Osteoporosis on the Structure, Remodeling and Mineralization of Bone

Effects of Different Regimens of Sodium Fluoride Treatment for Osteoporosis on the Structure, Remodeling and Mineralization of Bone

Drug-Induced Bone Loss

Patient-Specific Finite Element Analyses Detect Significant Mechanical Therapeutic Effects on Osteoporotic Vertebrae During a Three-Year Treatment

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