The Food and Drug Administration's Osteoporosis Guidance Document: Past, Present, and Future

Colman, Eric

doi:10.1359/jbmr.2003.18.6.1125

Cited by 30 publications

(22 citation statements)

References 6 publications

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“…It is worth noting here that the field of drug development for OA is currently analogous to osteoporosis 30 years ago [8], namely a disease in search of a robust gold standard outcome measure to inform clinical trials. The 1979 FDA Osteoporosis Guidelines acknowledged that evaluating the clinical effectiveness of osteoporosis drugs posed special challenges because of the “difficulties in assessing the state of skeletal bone quantitatively in vivo , the relatively small changes that are usually encountered and the duration of studies necessary to show significant effects” [8, 9].…”

Section: Introductionmentioning

confidence: 99%

“…The 1979 FDA Osteoporosis Guidelines acknowledged that evaluating the clinical effectiveness of osteoporosis drugs posed special challenges because of the “difficulties in assessing the state of skeletal bone quantitatively in vivo , the relatively small changes that are usually encountered and the duration of studies necessary to show significant effects” [8, 9]. By 1984, the FDA Osteoporosis Guidelines upgraded dual-energy photon absorptiometry from investigational to a valid and reliable method for measuring trabecular bone mass of the spine and this was critical to the subsequent approach to the development and regulation of osteoporosis drugs [8, 9]. OA is at a similar crossroads to which biomarkers may contribute substantively at this time.…”

Section: Introductionmentioning

confidence: 99%

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Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis

Kraus

Burnett

Coindreau

et al. 2011

Osteoarthritis and Cartilage

282

279

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Objective Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007–2009 at the behest of the Osteoarthritis Research Society International (OARSI FDA initiative). Results This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within one to two years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis

Kraus

Burnett

Coindreau

et al. 2011

Osteoarthritis and Cartilage

282

279

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“…Preclinical work in rats (Jiang et al, 1996b) confirmed the conclusions regarding the discrepancy between increases in bone mass and the expected increase in bone strength. Results from the work presented here directly assess the treatment-related impact on bone quality in preclinical models prior to clinical outcomes in support of the regulatory requirement guidance for the development of new osteoporosis drugs (FDA, 1994 Guidelines; Colmna, 2003). …”

Section: Discussionmentioning

confidence: 99%

Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis

et al. 2017

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The cathepsin K inhibitor odanacatib (ODN) is a potent and reversible inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. Previously, we described data on the treatment efficacy of ODN in a preclinical estrogen-deficient model of an ovariectomized (OVX) rhesus monkey using HR-pQCT based finite element analysis (FEA) in vivo estimates of bone strength on the distal radius. To support the bone safety profile of ODN, we report ex vivo data on the apparent and hard tissue biomechanical properties of the trabecular bone of vertebrae of animals after 20 months of dosing in three treatment groups: Vehicle (VEH), ODN (2 mg/kg/day), and ALN (30 μg/kg/week).Biomechanical axial compression tests were performed on cylindrical trabecular samples cored out of the third lumbar vertebra of each animal at the end of the study. The biomechanical test results demonstrated that a normal (positive correlation between bone mineral density and bone strength) apparent material property relationship was maintained in the lumbar spine of ODN and ALN treated non-human primates (NHP). Trabecular bone hard tissue Young's modulus value was estimated using experimentally measured stiffness combined with FEA. The FEA and experimental results demonstrated that ODN treatment for 20 months maintained normal trabecular bone material hard tissue properties in the OVX-monkeys and was comparable to ALN.

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“…There are two biomarkers, NTX1 and CTX1, used in osteoporosis research and clinical monitoring that are in fact in vitro diagnostics for osteoporosis. These, along with the advent, in 1979, of dual-energy photon absorptiometry as an FDA-approved method for quantifying bone mass of the spine, led to the rapid development of effective osteoporosis drugs [1]. OA currently is analogous to osteoporosis approximately 30 years ago-a disease in need of robust FDA-approved outcome measures to overcome the lack of appropriate tools for sensitively quantifying the state of the OA joint.…”

Section: Biomarkers Of Oamentioning

confidence: 99%

Patient Evaluation and OA Study Design: OARSI/Biomarker Qualification

Kraus

2012

HSS Journal®: The Musculoskeletal Journal of Hospital for Speci

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The Food and Drug Administration's Osteoporosis Guidance Document: Past, Present, and Future

Cited by 30 publications

References 6 publications

Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis

Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis

Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis

Patient Evaluation and OA Study Design: OARSI/Biomarker Qualification

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