Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk

Reginster, Jean‐Yves; Sarkar, Somnath; Zegels, Brigitte; Henrotin, Yves; Bruyère, Olivier; Agnusdei, D.; Collette, Julien

doi:10.1016/j.bone.2003.10.004

Cited by 101 publications

(53 citation statements)

References 31 publications

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“…When logistic regression analysis models were used to evaluate the relationship between the changes at 1 year in P1NP, OC, BALP, and urinary CTX and the risk of new vertebral fractures at 3 years, in the same study, a 1-year decrease in P1NP, BALP or OC but not urinary CTX was again predictive of the 3-year vertebral fracture risk reduction with raloxifene. The decrease in P1NP at 1 year accounted for 28% of the total reduction in vertebral fracture risk [32].…”

Section: Treatmentmentioning

confidence: 97%

“…Alendronate [10,17,18,19,20,21] Formation: BALP, PINP, PICP, OC Fracture, BMD Resorption: sCTX, uNTX, DPD Risedronate [12,22] Resorption: uDPD, uCTX, uNTX, Fracture, BMD Teriparatide [13,14,15,33] Formation: BALP, PICP, PINP Fracture, BMD Resorption: uDPD, uNTX, sCTX Raloxifene [30,31,32] Formation: BALP, PINP, OC Fracture Resorption: uCTX Early changes in BTM to monitor anti-osteoporosis therapy Similar to most chronic diseases, monitoring the efficacy of treatment of osteoporosis is a challenge. In contrast to BMD, which typically changes in response to therapy less than 2-5% per year, or a maximum of 3% in 3-6 months, most of osteoporosis therapies act by reducing or increasing individual BTM levels or their ratios by 30-200% within 3-6 months.…”

Section: Treatmentmentioning

confidence: 99%

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Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Reginster¹,

Collette²,

Neuprez³

et al. 2008

Bone

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Author's personal copy EditorialRole of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy AbstractMost of the currently available anti-osteoporosis medications promptly and significantly influence the rate of bone turnover. Biochemical markers of bone turnover now provide a high sensitivity to change, allowing the detection of these bone turnover changes within a couple of weeks. Since the anti-fracture efficacy of inhibitors of bone resorption or stimulators of bone formation appears to be largely independent of baseline bone turnover, biochemical markers do not appear to play a significant role in the selection of one particular drug, for an individual patient. However, there are consistent data showing that short-term changes in biochemical markers of bone turnover may be significant predictors of future changes in bone mineral density or fracture reduction, hence suggesting that bone turnover markers play a significant role in the monitoring of anti-osteoporosis therapy. © 2008 Elsevier Inc. All rights reserved.Keywords: Osteoporosis; Monitoring; Treatment; Bone density; Markers of bone turnover IntroductionClinical trials, conducted since the early nineties, have unequivocally shown the ability of several anti-osteoporosis medications to reduce fracture occurrence at various skeletal sites, including but not exhaustively the spine and hip [1]. Whereas the operational definition of osteoporosis is still based on a low bone mineral density (BMD), because low BMD is known to contribute to increased fracture risk, changes in bone mass and density, in response to anti-resorptive therapy, account for only a small portion of the predicted fracture risk reduction [2], a picture which may, however, be significantly changed with the availability of new therapies stimulating bone formation [3] or uncoupling bone formation from bone resorption [4].During the last decade, biochemical markers of bone turnover (BTM) have been developed, that are more sensitive than conventional ones for detecting abnormalities or changes of bone turnover rate [5]. Increased levels of bone resorption, and short-term changes in BTM, have been shown to predict the risk of fracture, independently of the level of BMD in untreated individuals [6,7].Dynamic changes in bone turnover, estimated by measurement of bone biochemical markers, such as breakdown products of type I collagen and proteins secreted by osteoblasts and osteoclasts in blood and urine, can also account for a major portion of antifracture efficacy of anti-resorptive or bone-forming agents [8]. Most of the currently marketed anti-osteoporos...

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Section: Treatmentmentioning

confidence: 97%

Section: Treatmentmentioning

confidence: 99%

Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Reginster¹,

Collette²,

Neuprez³

et al. 2008

Bone

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show abstract

“…In contrast, the effects of these anti-osteoporotic drugs on bone turnover differ greatly: bisphosphonates (figure 7), oestrogens, denosumab (figure 8), calcitonin, raloxifene tend to reduce bone resorption and bone formation in a dose dependent manner (88)(89)(90)(91)(92)(93)(94)(95)(96). Strontium ranelate, in contrast, has only subtle effects on bone turnover, showing a slight reduc- …”

Section: Bone Turnover Markers and Therapeutic Monitoringmentioning

confidence: 99%

Clinical application of biochemical markers of bone turnover

Seibel

2006

Arq Bras Endocrinol Metab

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With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This review provides an overview of the current evidence regarding the clinical use of biochemical markers of bone remodelling in bone disease, with an emphasis on osteoporosis. RESUMO Marcadores Bioquímicos da Remodelação Óssea.Tendo em vista o crescimento da população idosa na maioria dos paí-ses, os distúrbios do metabolismo ósseo e mineral estão tornando-se cada vez mais relevantes na prática clínica diária. Conseqüentemente, o interesse e a necessidade de medidas efetivas para serem usadas no rastreamento, diagnóstico e seguimento de tais patologias vêm crescendo acentuadamente. Além da avaliação clínica e de técnicas de imagens, os marcadores bioquímicos desempenham um importante papel na avaliação e diagnóstico das doenças ósseas metabólicas. Recentemente, a melhor caracterização dos componentes intracelulares e extracelulares da matriz óssea resultou no desenvolvimento dos marcadores moleculares, os quais refletem tanto a formação como a reabsorção óssea. Estes marcadores bioquímicos não são invasivos e comparativamente são de mais baixo custo, e quando aplicados e interpretados corretamente são instrumentos úteis no diagnóstico e tratamento das doenças ósseas metabólicas. Esta revisão abordará evidências atuais, levando em consideração o uso clínico dos marcadores bioquímicos da remodelação óssea nas doenças metabólicas ósseas, com ênfase na osteoporose.

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“…In clinical trials, the changes in bone turnover markers have been shown to be related to change in fracture risk [10] . There is evidence that there is an association between the change in bone formation markers but not bone resorption markers on raloxifene and the reduction in spine fracture risk [5,[11][12][13] . Changes in bone markers in response to treatment occur earlier and are of a greater magnitude than changes in bone density.…”

Section: Introductionmentioning

confidence: 99%

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

et al. 2016

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Introduction: The change in bone turnover markers (BTM) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene.Methods: Fifty postmenopausal osteopenic women, (age 51-72y) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40y). Bone mineral density (BMD) was measured at the spine and hip.Results: There was a decrease in BTM in response to raloxifene treatment; percentage change at 12 weeks, CTX -39% (95% CI -48 to -28) and PINP -32% (95% CI -40 to -23) P<0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was: CTX 38%, PINP 52%, at 48 weeks CTX 60%, PINP 65%. For the RI approach; at 12 weeks CTX and PINP 38%, at 48 weeks CTX 40%, PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene treated group compared to the no-treatment group at week 48; difference 0.031 g/cm2, (95% CI 0.016 to 0.046, P<0.001).Conclusions: The two approaches identified women that reached the target for treatment using BTM.Both LSC and RI criteria appear useful in identifying treatment response but the two approaches do not fully overlap and may be complementary.

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Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk

Cited by 101 publications

References 31 publications

Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Clinical application of biochemical markers of bone turnover

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

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