Efficacy of long-term fluoride and calcium therapy in correcting the deficit of spinal bone density in osteoporosis

Farley, S. M.; Libanati, Cesar; Odvina, Clarita V.; Smith, Lynna C.; Eliel, Leonard P.; Wakley, Glenn K.; Kilcoyne, Ray F.; Schulz, Eloy; Baylink, David J.

doi:10.1016/0895-4356(89)90048-6

Cited by 14 publications

(3 citation statements)

References 24 publications

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“…The anabolic effect of fluoride on the cancellous bone mineral mass of the axial skeleton has been repeatedly recorded in human studies, although large variations in the individual therapeutic response have also often been observed [47][48][49][50][51][52][53][54]. Nevertheless, this consistent anabolic effect on bone mass has not invariably been found to be associated with an increase in bone strength.…”

Section: Predictive Value Of Preclinical Studiesmentioning

confidence: 99%

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

Bonjour

Ammann

Rizzoli

1999

Osteoporosis International

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Osteoporosis, which is defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk, is a major health issue worldwide. Among the various strategies to prevent and cure this devastating ailment, an important objective is the development of new efficacious and safe drugs. This situation prompted the World Health Organization (WHO) to provide a comprehensive statement of guiding principles for the design, implementation and interpretation of both preclinical testing and clinical trials in osteoporosis. These guidelines, which are now available, underline the crucial importance of the preclinical evaluation, particularly for assessing the effect of an intervention on bone strength. This concept is heightened by the lack of a validated technique for noninvasively evaluating bone strength in humans and the multiple difficulties and heavy burden inherent in the evaluation of fracture rate in clinical trials. The WHO guidelines emphasize that a comprehensive and adequate preclinical program is expected to provide key information on the relationship between bone mass and strength and thus attenuate the burden of clinical studies. The present report provides a review of experimental evidence in support of the preclinical program as proposed in the WHO guidelines. This program is based on the recent development and refinement of animal models of osteoporosis that mimic the human condition according to the conceptual definition of the disease. Many preclinical studies carried out in appropriate animal models with agents that exert either antiresorbing or anabolic effects on bone indicate that they have been highly predictive of the drug action in humans in terms of both bone mass and remodeling, as well as of bone strength whenever fracture rate has been documented in clinical trials. Based on this evidence the WHO guidelines propose strategies according to which the results of preclinical evaluation will determine the end-points required in the different phases of the clinical development of the drug. Such a distribution of task assignment between preclinical and clinical programs should optimize the progress of research available to patients already suffering from or at risk of osteoporosis.

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Section: Predictive Value Of Preclinical Studiesmentioning

confidence: 99%

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

Bonjour

Ammann

Rizzoli

1999

Osteoporosis International

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“…[5] Armed with these methods, researchers have exposed several common medical practices as ineffective. For example, observational studies led us to believe that sodium fluoride reduced vertebral fractures, [7] that vitamin E reduced major coronary events, [8] and that high-dose aspirin was more effective than low-dose aspirin. [9] But subsequent randomized trials exposed all these treatments as useless or harmful.…”

Section: Introductionmentioning

confidence: 99%

The Need for Randomization in Animal Trials: An Overview of Systematic Reviews

et al. 2014

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Background and ObjectivesRandomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition.MethodsWe conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment.ResultsThirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinson's disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective.ConclusionsOur study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.

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“…The results of several studies using sodium fluoride in already-diagnosed cases of osteoporosis have been encouraging (Lundy et al, 1989;Pak et al, 1989;Riggs et al, 1990). The most consistent success has been in treatment of vertebral bone loss, often in conjunction with calcium supplementation (Farley et al, 1989;Heaney et al, 1989a-c;Hodsman and Drost, 1989;Mamelle et al, 1988). Kragstrup et al (1989) have had success using a combination of sodium fluoride, vitamin D, and calcium.…”

Section: Fluoridesmentioning

confidence: 99%

“Osteoporosis”: Etiologies, prevention, and treatment

Stini

1990

Am. J. Phys. Anthropol.

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W-ith the steady increase in life expectancies occurring in industrialized countries have come major changes in the causes of morbidity and mortality. The greatest burden on the health care delivery systems in these countries has shifted from the treatment of infectious diseases to extended care of degenerative conditions. One such condition of increasing widespread concern is osteoporosis. Chronic bone loss leading to fractures and secondary infections has become a major problem in the United States, and has been estimated to cost $6 to $8 billion annually.The etiology of osteoporosis is complex, depending upon the interaction of nutritional, endocrinological, and local factors that are subject to a variety of genetic and environmental influences. The stringent requirement of maintaining calcium homeostasis places heavy demands on the primary reservoir of calcium, the skeleton, when intake andlor absorption are inadequate. Inactivity, depriving bone of its weight-bearing function, also initiates bone resorption. Under normal circumstances in the young adult, bone is maintained through continual, balanced turnover of mineral and calcium. When this balance is upset, loss of bone can be slow or rapid, reversible or irreversible. The trabecular compartment with its high surface-to-volume ratio is most rapidly mobilized, but cortical bone is ultimately resorbed as well.Involationaf osteoporosis is conventionally designated as either type i I postmenopauqali or type I1 senile:. Women are affected by both and, because of a generally less-robust skeleton, experience risk of fracture earlier than men on the average. The hormonal and physiological factors involved in the regulation of normal bone physiology and the factors leading to loss of bone mass constitute a n area of active research that is casting light on the fundamental mechanisms underlying bone growth and maintenance in the search for new avenues of prevention and treatment of osteoporosis.Currently the fastest growing segment of the population of the United States is the age group 85 years old and older (United Nations, 1986). The increasing numbers of elderly citizens of both sexes have changed the country's demographic profile but the proportion of women living to advanced age has had singular impact. In North America in 1984, males outnumbered females by about 1 million (29 million to 28 million) up to the age of 15 years, but in the age group 65 years old and older, females outnumbered males by 6 million (18 million women, 12 million men) (Stini, 1987). Beyond age 65 years, the disparity in survival continues to grow. In the age group 80 to 84 years, the death rate is currently 107.0 per 1,000 for males and 66.9 per 1,000 for females. Thus, the population of the United States 0 1990 Wiley-Liss, Inc.

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Efficacy of long-term fluoride and calcium therapy in correcting the deficit of spinal bone density in osteoporosis

Cited by 14 publications

References 24 publications

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

Importance of Preclinical Studies in the Development of Drugs for Treatment of Osteoporosis: A Review Related to the 1998 WHO Guidelines

The Need for Randomization in Animal Trials: An Overview of Systematic Reviews

“Osteoporosis”: Etiologies, prevention, and treatment

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