Abstract
Summary
The aim of this systematic review and meta-analysis is to study the utility of the commonly used bone turnover markers in evaluating disease activity in patients with Paget’s disease of bone before and after treatment with bisphosphonates. We found good correlation between the bone turnover marker concentrations and disease activity assessed by bone scintigraphy.
Introduction
Paget’s disease of bone is a common skeletal disorder of the elderly. Bone turnover marker concentrations are used for diagnosis and follow-up. We aimed to compare the available bone turnover markers and determine their utility in assessing disease activity when compared to quantitative bone scintigraphy.
Methods
We conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. We evaluated total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase (bone ALP), procollagen type 1 amino-terminal propeptide (P1NP), serum, and urine C-terminal telopeptide (uCTx and sCTx, respectively), and urine N-terminal telopeptide (uNTx). The main outcome of interest was the correlation of disease activity with concentrations of bone turnover markers in Paget’s disease patients before and after treatment with bisphosphonates. Correlation coefficients were pooled across studies using the random effects model.
Results
We included 17 observational studies and one trial reporting on 953 patients. Prior to treatment, all studied bone turnover markers had moderate to strong correlation with scintigraphic indices (correlation coefficients ranging from 0.58 to 0.80) with no statistically significant difference between the bone turnover markers overall (p = 0.08). P1NP, uNTx, and bone ALP tend to have higher correlation with scintigraphy. After starting treatment with bisphosphonate, there was moderate to strong correlation with disease activity with all markers except bone ALP (correlation coefficients ranging from 0.43 to 0.70).
Conclusion
The findings of this meta-analysis suggest the Paget’s disease activity is best monitored by following P1NP levels. However, total ALP, bone ALP, and uNTx are good alternatives as markers of disease activity in untreated patients. Total ALP and uNTx can be useful in following patients with Paget’s disease after treatment if P1NP is not available. Clinicians, however, should take availability, cost, and the presence of liver disease into consideration when deciding which bone turnover marker is most appropriate when evaluating patients with Paget’s disease.
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Acknowledgments
This study was supported by a contract from the Endocrine Society.
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Appendix 1
Appendix 1
Search strategy
Ovid
Database(s)
EMBASE 1988 to 2012 Week 42, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) 1946 to Present, EBM Reviews - Cochrane Central Register of Controlled Trials October 2012, EBM Reviews - Cochrane Database of Systematic Reviews 2005 to September 2012
Scopus
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1
TITLE-ABS-KEY(“Osteitis Deformans” or (paget W/4 bone) or (pagets W/4 bone) or “ostitis deformans”)
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2
TITLE-ABS-KEY(“biological marker*” or biomarker* or “serum marker*” or “laboratory marker*” or “immunologicmarker*” or (surrogate W/1 endpoint*) or (surrogate W/1 “end point*”) or “biologic marker*” or “immune marker*” or “clinical marker*” or “biochemical marker*” or “biological indicator*” or bioindicator* or “Alkaline Phosphatase”or “alcalic phosphatase” or “alkali phosphatase” or “alkalic phosphatase” or “alkaline monophosphoesterase” or “alkaline phosphohydrolase” or “alkaline phosphomonoesterase” or “alkalinic phosphatase” or “basic phosphatase” or “orthophosphoric monoester phosphohydrolase” or procollagen or “collagen precursor” or “proto-collagen” or protocollagen or precollagen or “collagen type 1” or “collagen 1” or “collagen i” or “type 1 collagen” or vitrogen or “type I collagen” or P1NP or P1NP or telopeptide or creatinine or creatinin or kreatinine or methylglycocyamimine or “1 methylglycocyamidine” or “1 methylhydantoin 1 imide” or “2 imino 1 methyl 4imidazolinone”)
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3
TITLE-ABS-KEY(serum or blood or urine or urinary)
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4
TITLE-ABS-KEY( (evidence W/1 based) OR (meta W/1 analys*) OR (systematic* W/2 review*) OR guideline OR (control* W/2 stud*) OR (control* W/2 trial*) OR (randomized W/2 stud*) OR (randomized W/2 trial*) or random* or “latin square” or crossover or “cross-over” or placebo* or (doubl* N5 blind*) or (doubl* N5 mask*) or (singl* N5 blind*) or (singl* N5 mask*) or (tripl* N5 blind*) or (tripl* N5 mask*) or (trebl* N5 blind*) or (trebl* N5 mask*) or “comparative study” OR “comparative survey” OR “comparative analysis” OR “cohort study” OR “cohort survey” OR “cohort analysis” OR “longitudinal study” OR “longitudinal survey” OR “longitudinal analysis” OR “retrospective study” OR “retrospective survey” or “retrospective analysis” OR “prospective study” OR “prospective survey” OR “prospective analysis” OR “population study” OR “population survey” OR “population analysis” OR “concurrent study” OR “concurrent survey” OR “concurrent analysis” or “incidence study” OR “incidence survey” OR “incidence analysis” OR “follow-up study” OR “follow-up survey” OR “follow-up analysis” or “observational study” OR “observational survey” OR “observational analysis” OR “case study” OR “case series” OR “clinical series” OR “case studies” or “clinical study” OR “clinical trial” or “evaluation study” OR “evaluation survey” OR “evaluation analysis” or “twin study” OR “twin survey” OR “twin analysis” or “validation study” OR “validation survey” OR “validation analysis” or “experimental study” OR “experimental analysis” or “field study” OR “field survey” OR “field analysis” or “in vivo study” OR “in vivo analysis” or “panel study” OR “panel survey” OR “panel analysis” or “pilot study” OR “pilot survey” OR “pilot analysis” or “prevention study” OR “prevention survey” OR “prevention analysis” or “replication study” OR “replication analysis” or “theoretical study” OR “theoretical analysis” or “trend study” OR “trend survey” OR “trend analysis” or “multivariate analysis”)
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5
1 and 2 and 3 and 4
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6
PMID (0*) OR PMID (1*) OR PMID (2*) OR PMID (3*) OR PMID (4*) OR PMID (5*) OR PMID (6*) OR PMID (7*) OR PMID (8*) OR PMID (9*)
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7
5 and not 6
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DOCTYPE(le) OR DOCTYPE(ed) OR DOCTYPE(bk) OR DOCTYPE(er) OR DOCTYPE(no) OR DOCTYPE(sh)
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9
7 and not 8
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Al Nofal, A.A., Altayar, O., BenKhadra, K. et al. Bone turnover markers in Paget’s disease of the bone: A Systematic review and meta-analysis. Osteoporos Int 26, 1875–1891 (2015). https://doi.org/10.1007/s00198-015-3095-0
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DOI: https://doi.org/10.1007/s00198-015-3095-0