Response of Biochemical Markers of Bone Turnover to Hormone Replacement Therapy: Impact of Biological Variability

Hannon, Rosemary A.; Blumsohn, Aubrey; Naylor, Kim; Eastell, Richard

doi:10.1359/jbmr.1998.13.7.1124

Cited by 250 publications

(174 citation statements)

References 36 publications

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“…Urine NTX is more variable than serum assays, and the measurement of creatinine adds to the 'noise', and increases the LSC [27,33] . The LSC values were calculated using a two tailed approach and were comparable with those of Fink et al for PINP CTX and NTX, and Hannon et al for NTX [20,34] , but some were higher than reported by others [20,21] . Differences between studies include the participants that the LSC is calculated from, and type of assay.…”

Section: Discussionsupporting

confidence: 68%

“…Firstly there is the least significant change approach (LSC) signifying the minimum change in BTM that can be attributed to treatment effect rather than random variation of the marker (usually with 95% certainty). This is most commonly expressed as a percentage change [20,21] or alternatively as absolute units [22] ; the target for treatment with bisphosphonates being to reduce the bone markers by at least the LSC. The second approach is that the target for treatment is to decrease the BTM to the lower half of the premenopausal reference interval (RI) [9,23] .…”

Section: Introductionmentioning

confidence: 99%

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Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

et al. 2015

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Introduction: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers.Methods: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomized to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for two years. The LSC for each marker was derived within the study population whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years).Results: Over 70% of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63% (difference 13%, 95%CI 0 to 27.1, P=0.049) and good compliance -67% (difference 15.9%, 95%CI 6.3 to 25.5, P=0.001). Responders had a greater increase in spine bone density compared to non-responders; for example 6.2% vs. 2.3%, (difference 3.9%, 95%CI 1.6 to 6.3, p=0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate.Conclusions: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.Key words: postmenopausal osteoporosis, bone turnover markers, variability, bisphosphonate Mini Abstract (50 words)We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis.Response was more likely with alendronate and ibandronate, than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80% of her medication.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

et al. 2015

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“…Urinary resorption markers have several limitations, including the need for control of sampling time and correction for urinary creatinine, and a large within patient variability (Garnero et al, 1994;Hannon et al, 1998). Urinary collection is, moreover, often cumbersome in clinical practice.…”

Section: Resultsmentioning

confidence: 99%

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Garnero

Buchs

Zekri³

et al. 2000

Br J Cancer

215

128

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Prostate cancer is the most common malignancy in elderly men and is often complicated by osteosclerotic metastases. Bone scintigraphy is commonly used to assess the extent of bone metastases; its use is limited in monitoring of treatment efficacy because it is an expensive, time-consuming technique that does not reflect the rapid skeletal response to therapy (Coleman, 1998). The bone scan flare response following successful therapy also reduces the value of bone scanning in the early monitoring of treatment in prostate cancer (Pollen et al, 1984). The serum level of prostatespecific antigen is the most sensitive index of disease progression in most but not all patients, but does not reflect the effects of palliative treatments such as bisphosphonates for bone metastases in patients that escape from antihormonal therapy.The marked increase of osteoblastic activity in patients with osteosclerotic metastases is reflected by increased levels of serum total and bone-specific alkaline phosphatase (Pecherstorfer et al, 1995;Lorente et al, 1996). There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).In this study we assessed the level of bone resorption in patients with osteosclerotic metastases from prostate cancer before and after bisphosphonate treatment by using new sensitive and specific biochemical markers of bone resorption including a serum assay for type I collagen C-telopeptide breakdown products; and values were compared to those of bone formation markers. PATIENTS AND METHODSForty-eight patients with carcinoma of the prostate (age 71.7 ± 9.6 years, mean ± 1 s.d.) and nine with benign prostatic hyperplasia (BHP) (age 69.8 ± 4.2 years) were enrolled. All patients with cancer had a prostatic biopsy and tissue diagnosis of adenocarcinoma. Bone involvement and its extent was evaluated by bone scintigraphy using Technetium-99m labelled methylene bisphosphonate. When bone metastases were suspected, confirmation was obtained with standard radiographs, computerized tomography (CT) and/or magnetic resonance imaging. The metastatic load in Summary Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to tha...

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“…Serum TRAP however, was shown to be a poor indicator of bone turnover in response to antiresorptive therapy. 48 Brehme et al 15 noted that much of the TRAP in the circulation forms inactive complexes with the proteinase inhibitor ␣2-macroglobulin, which may confound the use of TRAP as a marker of bone turnover. Recently, a new serum TRAP assay has been developed that combines enzyme capture with the monoclonal antibody O1A and isoform 5b-specific assay conditions.…”

Section: Correlation Between Trap Activity and Bone Resorptionmentioning

confidence: 99%

Structure, function, and regulation of tartrate-resistant acid phosphatase

Oddie

Schenk

Angel

et al. 2000

Bone

198

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Response of Biochemical Markers of Bone Turnover to Hormone Replacement Therapy: Impact of Biological Variability

Cited by 250 publications

References 36 publications

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Structure, function, and regulation of tartrate-resistant acid phosphatase

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