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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2017

Open Access 01-12-2017 | Research article

A 12-week randomized, double-blind, placebo-controlled multicenter study of choline-stabilized orthosilicic acid in patients with symptomatic knee osteoarthritis

Authors: Piet Geusens, Karel Pavelka, Jozef Rovensky, Johan Vanhoof, Nathalie Demeester, Mario Calomme, Dirk Vanden Berghe

Published in: BMC Musculoskeletal Disorders | Issue 1/2017

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Abstract

Background

The aim of this study was to assess the efficacy of choline-stabilized orthosilicic acid (ch-OSA) in patients with symptomatic knee osteoarthritis (OA).

Methods

In a multicenter, double-blind, placebo-controlled study, 211 patients with knee OA (Kellgren and Lawrence grade II or III) and moderate to moderately severe pain were randomly allocated to ch-OSA or placebo for 12 weeks. The primary outcome was the change in the WOMAC pain subscale from baseline to week 12. Secondary outcomes were changes from baseline to week 12 in WOMAC total, WOMAC stiffness, WOMAC physical function, Subject Global Assessment and levels of cartilage degradation biomarkers C-terminal telopeptide of collagen type II (CTX-II) and cartilage oligomeric matrix protein (COMP). Pre-specified subgroup analyses included the effect of gender.

Results

A total of 166 (120 women, 46 men) patients were included in the analysis (87 and 79 in the ch-OSA and placebo group, respectively). In the total study population, no differences were observed between the two treatment groups for the different outcomes but significant treatment x gender interactions were found. In men taking ch-OSA, a significant improvement in WOMAC total, WOMAC stiffness and WOMAC physical function as well as a lower increase in biomarker levels of cartilage degradation was observed, but not in women. The change in WOMAC pain showed a similar positive trend in men taking ch-OSA.

Conclusion

After 12 weeks of treatment, no effect was found of ch-OSA in the total study population on clinical parameters and biomarkers, but a gender interaction was observed. In men, ch-OSA was found effective in reducing symptoms of knee OA, which was associated with a slight but significant reduction of biomarkers that are related to cartilage degradation.

Trial registration

The study was registered retrospectively: ISRCTN88583133. Registration date: 2015-10-07.
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Literature
1.
2.
Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. OsteoarthrCartil. 2007;15:981–1000.
3.
Kraus VB, Burnett B, Coindreau J, Cottrell S, Eyre D, Gendreau M, et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthr Cartil. 2011;19:515–42.CrossRefPubMedPubMedCentral
4.
Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133:635–46.CrossRefPubMed
5.
Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377:2115–26.CrossRefPubMed
6.
Lafeber FP, van Laar JM. Strontium ranelate: ready for clinical use as disease-modifying osteoarthritis drug? Ann Rheum Dis. 2013;72:157–61.CrossRefPubMed
7.
Losina E, Weinstein AM, Reichmann WM, Burbine SA, Solomon DH, Daigle ME, et al. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res. 2013;65:703–11.CrossRef
8.
9.
Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthr Cartil. 2005;13:769–81.CrossRefPubMed
10.
Guermazi A, Hunter DJ, Roemer FW. Plain radiography and magnetic resonance imaging diagnostics in osteoarthritis: validated staging and scoring. J Bone Joint Surg Am. 2009;91 Suppl 1:54–62.CrossRefPubMed
11.
van Spil WE, DeGroot J, Lems WF, Oostveen JC, Lafeber FP. Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria. Osteoarthr Cartil. 2010;18:605–12.CrossRefPubMed
12.
Lotz M, Martel-Pelletier J, Christiansen C, Brandi ML, Bruyere O, Chapurlat R, et al. Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis. 2013;72:1756–63.CrossRefPubMedPubMedCentral
13.
Bauer DC, Hunter DJ, Abramson SB, Attur M, Corr M, Felson D, et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthr Cartil. 2006;14:723–7.CrossRefPubMed
14.
Spector TD, Calomme MR, Anderson SH, Clement G, Bevan L, Demeester N, et al. Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. BMC Musculoskelet Disord. 2008;9:85.CrossRefPubMedPubMedCentral
15.
Barel A, Calomme M, Timchenko A, De Paepe K, Demeester N, Rogiers V, et al. Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin. Arch Dermatol Res. 2005;297:147–53.CrossRefPubMed
16.
17.
Toohey JI. Homocysteine toxicity in connective tissue: theories, old and new. Connect Tissue Res. 2008;49:57–61.CrossRefPubMed
18.
Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29:1039–49.CrossRefPubMed
19.
20.
Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–40.PubMed
21.
Leys C, Ley C, Klein O, Bernard P, Licata L. Detecting outliers: do not use standard deviation around the mean, use absolute deviation around the median. J Exp Soc Psychol. 2013;49:764–6.CrossRef
22.
Ziegler D, Pritchett YL, Wang F, Desaiah D, Robinson MJ, Hall JA, et al. Impact of disease characteristics on the efficacy of duloxetine in diabetic peripheral neuropathic pain. Diabetes Care. 2007;30:664–9.CrossRefPubMed
23.
Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62:1145–55.CrossRefPubMedPubMedCentral
24.
Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil. 2008;16:137–62.CrossRefPubMed
25.
Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2012;64:465–74.CrossRef
26.
McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22:363–88.CrossRefPubMed
27.
Geusens P, Lems W. Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis. Ther Clin Risk Manag. 2008;4:337–44.CrossRefPubMedPubMedCentral
28.
Thaler R, Agsten M, Spitzer S, Paschalis EP, Karlic H, Klaushofer K, et al. Homocysteine suppresses the expression of the collagen cross-linker lysyl oxidase involving IL-6, Fli1, and epigenetic DNA methylation. J Biol Chem. 2011;286:5578–88.CrossRefPubMed
29.
Zhang Q, Li H, Zhang Z, Yang F, Chen J. Serum metabolites as potential biomarkers for diagnosis of knee osteoarthritis. Dis Markers. 2015;2015:684794.PubMedPubMedCentral
30.
Jugdaohsingh R, Watson AI, Pedro LD, Powell JJ. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover. Bone. 2015;75:40–8.CrossRefPubMedPubMedCentral
31.
Calomme M, Geusens P, Demeester N, Behets GJ, D’Haese P, Sindambiwe JB, et al. Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid. Calcif Tissue Int. 2006;78:227–32.CrossRefPubMed
32.
Spector TD, Conaghan PG, Buckland-Wright JC, Garnero P, Cline GA, Beary JF, et al. Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Arthritis Res Ther. 2005;7:R625–33.CrossRefPubMedPubMedCentral
33.
34.
McAlindon TE, Snow S, Cooper C, Dieppe PA. Radiographic patterns of osteoarthritis of the knee joint in the community: the importance of the patellofemoral joint. Ann Rheum Dis. 1992;51:844–9.CrossRefPubMedPubMedCentral
35.
36.
Smith YR, Stohler CS, Nichols TE, Bueller JA, Koeppe RA, Zubieta JK. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci. 2006;26:5777–85.CrossRefPubMedPubMedCentral
37.
Hanna FS, Teichtahl AJ, Wluka AE, Wang Y, Urquhart DM, English DR, et al. Women have increased rates of cartilage loss and progression of cartilage defects at the knee than men: a gender study of adults without clinical knee osteoarthritis. Menopause. 2009;16:666–70.CrossRefPubMed
38.
van Spil WE, Drossaers-Bakker KW, Lafeber FP. Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: data from CHECK, a cohort study of early osteoarthritis. Ann Rheum Dis. 2013;72:29–36.CrossRefPubMed
39.
40.
Calvo E, Castaneda S, Largo R, Fernandez-Valle ME, Rodriguez-Salvanes F, Herrero-Beaumont G. Osteoporosis increases the severity of cartilage damage in an experimental model of osteoarthritis in rabbits. Osteoarthr Cartil. 2007;15:69–77.CrossRefPubMed
41.
Wang CJ, Huang CY, Hsu SL, Chen JH, Cheng JH. Extracorporeal shockwave therapy in osteoporotic osteoarthritis of the knee in rats: an experiment in animals. Arthritis Res Ther. 2014;16:R139.CrossRefPubMedPubMedCentral
42.
Reginster JY, Kvasz A, Bruyere O, Henrotin Y. Is there any rationale for prescribing hormone replacement therapy (HRT) to prevent or to treat osteoarthritis? Osteoarthr Cartil. 2003;11:87–91.CrossRefPubMed
43.
Kwan Tat S, Lajeunesse D, Pelletier JP, Martel-Pelletier J. Targeting subchondral bone for treating osteoarthritis: what is the evidence? Best Pract Res Clin Rheumatol. 2010;24:51–70.CrossRefPubMed
44.
45.
European Food Safety Authority (EFSA). Scientific opinion of the panel on food additives and nutrient sources added to food on choline-stabilised orthosilicic acid added for nutritional purposes to food supplements following a request from the European Commission. EFSA J. 2009;948:1–23.
46.
Reginster JY, Badurski J, Bellamy N, Bensen W, Chapurlat R, Chevalier X, et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial. Ann Rheum Dis. 2013;72:179–86.CrossRefPubMed
47.
Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martin-Mola E, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007;56:555–67.CrossRefPubMed
48.
Geusens P, Chapurlat R, Schett G, Ghasem-Zadeh A, Seeman E, de Jong J, et al. High-resolution in vivo imaging of bone and joints: a window to microarchitecture. Nat Rev Rheumatol. 2014;10:304–13.CrossRefPubMed
Metadata
Title
A 12-week randomized, double-blind, placebo-controlled multicenter study of choline-stabilized orthosilicic acid in patients with symptomatic knee osteoarthritis
Authors
Piet Geusens
Karel Pavelka
Jozef Rovensky
Johan Vanhoof
Nathalie Demeester
Mario Calomme
Dirk Vanden Berghe
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2017
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-016-1370-7

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