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ABSTRACT: The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered a cost-effective strategy compared with no treatment for the treatment of osteoporotic men from a Belgian healthcare payer perspective. INTRODUCTION: This study was conducted to estimate the cost-effectiveness of strontium ranelate in the treatment of osteoporotic men. METHODS: A previously validated Markov microsimulation model was adapted to estimate the cost ( 2,010) per quality-adjusted life-year (QALY) gained of strontium ranelate compared with no treatment. Similar efficacy data on lumbar spine and femoral neck bone mineral density (BMD) between men with osteoporosis at high risk of fracture (MALEO Trial) and postmenopausal osteoporotic women (pivotal SOTI, TROPOS trials) supports the assumption, in the base-case analysis, of the same relative risk reduction of fractures in men as for women. Analyses were conducted, from a Belgian healthcare payer perspective, in the population from the MALEO Trial who is a men population with a mean age of 73 years, and BMD T-score ≤-2.5 or prevalent vertebral fracture (PVF). RESULTS: In the MALEO population, strontium ranelate compared with no treatment was estimated at 49,798 and 25,584 per QALY gained using efficacy data from the intent-to-treat analysis and the per-protocol analysis including only adherent patients, respectively. In men with a BMD T-score ≤-2.5 or with PVF, the cost per QALY gained of strontium ranelate fall below thresholds of 45,000 and 25,000 per QALY gained based on efficacy data from the entire population of the clinical trial and from the per-protocol analyses, respectively. CONCLUSIONS: The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered cost-effective compared with no treatment for male osteoporosis.
Osteoporosis International 02/2013; · 4.58 Impact Factor
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ABSTRACT: Abstract Background Vitamin D insufficiency has deleterious consequences on health outcomes. In elderly or postmenopausal women, it may exacerbate osteoporosis. Scope There is currently no clear consensus on definitions of vitamin D insufficiency or minimal targets for vitamin D concentrations and proposed targets vary with the population. In view of the potential confusion for practitioners on when to treat and what to achieve, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) convened a meeting to provide recommendations for clinical practice, to ensure the optimal management of elderly and postmenopausal women with regard to vitamin D supplementation. Findings Vitamin D has both skeletal and extra-skeletal benefits. Patients with serum 25-hydroxyvitamin D (25-(OH)D) levels <50 nmol/L have increased bone turnover, bone loss, and possibly mineralization defects compared with patients with levels >50 nmol/L. Similar relationships have been reported for frailty, nonvertebral and hip fracture, and all-cause mortality, with poorer outcomes at <50 nmol/L. Conclusion The ESCEO recommends that 50 nmol/L (i.e. 20 ng/mL) should be the minimal serum 25-(OH)D concentration at the population level and in patients with osteoporosis to ensure optimal bone health. Below this threshold, supplementation is recommended at 800 to 1000 IU/day. Vitamin D supplementation is safe up to 10 000 IU day (upper limit of safety) (resulting in an upper limit of adequacy of 125 nmol/L 25-(OH)D). Daily consumption of calcium- and vitamin D-fortified food products (e.g. yoghurt or milk) can help improve vitamin D intake. Above the threshold of 50 nmol/L, there is no clear evidence for additional benefits of supplementation. On the other hand, in fragile elderly subjects who are at elevated risk for falls and fracture, the ESCEO recommends a minimal serum 25-(OH)D level of 75 nmol/L (i.e. 30 ng/mL), for the greatest impact on fracture.
Current Medical Research and Opinion 01/2013; · 2.38 Impact Factor
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ABSTRACT: OBJECTIVE: Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA). DESIGN: Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) ≥ 7 and pain ≥ 40 mm on a visual analogical scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure. RESULTS: After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (<0.001) and VAS (P < 0.01). No significant difference in terms of security and tolerability was observed between the three groups. CONCLUSION: This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient.
Osteoarthritis and Cartilage 10/2012; · 3.90 Impact Factor
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ABSTRACT: Background/Aims: Bone mass density values have been related with risk of vertebral fractures in post-menopausal women. However, bone mass density is not perfectly accurate in predicting risk of fracture, which decreases its usefulness as a surrogate in clinical trials. We propose a modeling framework with three interconnected parts to improve the evaluation of bone mass density accuracy in forecasting fractures after treatment.Methods: The modeling framework includes: (1) a piecewise regression to describe non-linear temporal BMD changes more accurately than crude percent changes, (2) a structural equation model to analyze interdependencies among vertebral fractures and their potential risk factors in preference to regression techniques that consider only directional associations, and (3) a counterfactual causal interpretation of the direct and indirect relationships between treatment and occurrence of vertebral fractures. We apply the methods to BMD repeated measurements from a study of the effect of bazedoxifene acetate on incident vertebral fractures in three different geographical regions.Results: We made four observations: (1) bone mass density changes varied largely across participants, (2) baseline age and body mass index influenced baseline bone mass density that, in turn, had an effect on prevalent fractures, (3) direct and/or indirect effects of bazedoxifene acetate on incident fractures were different across regions, and (4) estimates of indirect effects were sensible to the presence of post-treatment unmeasured confounders. In one region, around 40% of the bazedoxifene acetate effect on the occurrence of fracture is explained by its effect on bone mass density. Under the counterfactual approach, these 40% represent the average difference in the occurrence of fracture observed for untreated individuals when their bone mass density values are set at the value under bazedoxifene acetate versus under placebo.Conclusions: Computational methods are available to evaluate and interpret the surrogacytic capability of a biomarker of a primary outcome.
Statistical Methods in Medical Research 09/2012; · 2.44 Impact Factor
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ABSTRACT: The FRAX(®) tool that calculates the 10-year probability of having a fracture has recently been validated for Belgium. Little is known about the perception and knowledge that GPs have about this tool in their daily practice. A survey has been conducted as part of a screening campaign for various diseases. The primary objective of the present study was to assess the perception and the knowledge of the FRAX(®) tool by GPs. The secondary objective was to assess the impact of an information brochure about the FRAX(®) tool on these outcomes. The survey was sent to a sample of 700 GPs after only half of them had received the information brochure. The survey results show that, out of the 193 doctors who responded to the survey, one-third know the FRAX(®) tool but less than 20 % use it in their daily clinical practice. Among those who use it, the FRAX(®) tool is largely seen as a complementary but not as an essential tool in the diagnosis or in the management of osteoporosis. It appears that the brochure could improve the knowledge of the FRAX(®) tool but it would not be more efficient on its use in daily practice than the other sources of information. At present, the use of the FRAX(®) tool in Belgium is limited but an information brochure could have a positive impact on the knowledge of the FRAX(®) tool.
Rheumatology International 07/2012; · 1.88 Impact Factor
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ABSTRACT: To assess health-related quality of life (HRQOL) in a prospective study with 7 years of follow-up in 49 consecutive patients who underwent a total joint replacement because of osteoarthritis.
Generic HRQOL was assessed with the short-form 36 (SF-36) and specific HRQOL with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
Out of the 39 subjects who have completed the 7 years of follow-up of this study, 22 (56.4 %) underwent a hip replacement surgery and the other 17 (43.6 %) a knee replacement. Six months after surgery, a significant improvement, compared to preoperative scores, was observed in two of the eight dimensions of the SF-36 (i.e. physical function and pain). The same dimensions, pain and physical function, at the same time, 6 months after surgery, measured by the WOMAC, showed a significant improvement as well, but there was no significant change in the stiffness score. From 6 months to the end of follow-up, changes in SF-36 scores showed a significant improvement in physical function (p = 0.008), role-physical (p = 0.004) and role-emotional (p = 0.01) while all scores of the WOMAC improved (p < 0.001 for pain, p < 0.001 for stiffness and p < 0.01 for physical function).
The improvements observed in HRQOL at short term after surgery, are at least maintained over a 7-year follow-up period.
Archives of Orthopaedic and Trauma Surgery 07/2012; 132(11):1583-7. · 1.37 Impact Factor
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ABSTRACT: To assess the number of anti-osteoporosis treatments that would be reimbursed by the Belgian social security if either FRAX(®) or the current criteria were used to determine access to reimbursement. This is a retrospective study based on data from 1,000 women randomly selected from an outpatient hospital specialized in bone metabolism in Belgium. Proportions of potentially refunded treatments between FRAX(®) and current criteria were compared. Out of the 1,000 women files, 890 have sufficient information to assess FRAX(®). In Belgium, current criteria include a bone mineral density (BMD) T score below -2.5 at the lumbar spine, the femoral neck or the total hip and/or at least a prevalent vertebral fracture. Using these criteria, 167 women (18.8 %) would have access to reimbursement. Using the criteria based on the validated Belgian FRAX(®) tool, only 116 women (13.0 %) would have access to reimbursement, meaning that access to reimbursement based on FRAX(®) criteria would reduce by 30 % the anti-osteoporosis drug expenses covered by the national social security. Interestingly, only 65 women out of the 116 (56.0 %) selected with the FRAX(®) criteria were also selected with the current criteria of the national social security. A substantial proportion of individuals that would potentially receive a reimbursement for their treatment using the FRAX(®) criteria do not have access to any refund for their treatment with the current criteria. Since patients identified with the FRAX(®) tool are those with the highest risk profile for future fractures, reappraisals of treatment reimbursement guidelines are expected in Belgium.
Rheumatology International 07/2012; · 1.88 Impact Factor
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ABSTRACT: Evaluation of the efficacy and safety of a food supplement made of collagen hydrolysate 1200 mg/day versus placebo during 6 months, in subjects with joint pain at the lower or upper limbs or at the lumbar spine.
Comparative double-blind randomized multicenter study in parallel groups.
200 patients of both genders of at least 50 years old with joint pain assessed as ≥30 mm on a visual analogical scale (VAS).
Collagen hydrolysate 1200 mg/day or placebo during 6 months.
Comparison of the percentage of clinical responder between the active collagen hydrolysate group and the placebo group after 6 months of study. A responder subject was defined as a subject experiencing a clinically significant improvement (i.e. by 20% or more) in the most painful joint using the VAS score. All analyses were performed using an intent-to-treat procedure.
At 6 months, the proportion of clinical responders to the treatment, according to VAS scores, was significantly higher in the collagen hydrolysate (CH) group 51.6%, compared to the placebo group 36.5% (p<0.05). However, there was no significant difference between groups at 3 months (44.1% vs. 39.6%, p=0.53). No significant difference in terms of security and tolerability was observed between the two groups.
This study suggests that collagen hydrolysate 1200 mg/day could increase the number of clinical responders (i.e. improvement of at least 20% on the VAS) compared to placebo. More studies are needed to confirm the clinical interest of this food supplement.
Complementary therapies in medicine 06/2012; 20(3):124-30. · 1.95 Impact Factor
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R Rizzoli,
C Cooper,
J-Y Reginster,
B Abrahamsen,
J D Adachi,
M L Brandi, O Bruyère,
J Compston,
P Ducy,
S Ferrari,
N C Harvey,
J A Kanis,
G Karsenty,
A Laslop,
V Rabenda,
P Vestergaard
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ABSTRACT: Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures.
Bone 05/2012; 51(3):606-13. · 4.02 Impact Factor
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ABSTRACT: It has been shown that antidepressants would have a direct action on bone metabolism and would be associated with increased fracture risk. Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types. INTRODUCTION: This study seeks to investigate the relationship between use of antidepressants and the risk of fracture. METHODS: An exhaustive systematic research of case-control and cohort studies published or performed between 1966 and April 2011 that reported risk estimates of fracture associated with use of antidepressants was performed using MEDLINE, PsycINFO, and the Cochrane Systematic Review Database, manual review of the literature, and congressional abstracts. Inclusion, quality scoring, and data abstraction were performed systematically by three independent reviewers. RESULTS: A total of 34 studies (n = 1,217,464 individuals) were identified. Compared with non-users, the random effects pooled RR of fractures of all types, among antidepressant users, were 1.39 (95%CI 1.32-1.47). Use of antidepressants were associated with a 42 %, 47 %, and 38 % risk increase in non-vertebral, hip, and spine fractures, respectively ([For non-vertebral fractures: RR = 1.42, 95%CI 1.34-1.51]; [For hip fractures: RR = 1.47, 95%CI 1.36-1.58]; [For spine fractures: RR = 1.38, 95%CI 1.19-1.61]). Studies examining SSRI use showed systematically a higher increase in the risk of fractures of all types, non-vertebral, and hip fractures than studies evaluating TCA use. CONCLUSIONS: Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types.
Osteoporosis International 05/2012; · 4.58 Impact Factor
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S. Vasikaran,
R. Eastell, O. Bruyère,
A. J. Foldes,
P. Garnero,
A. Griesmacher,
M. McClung,
H. A. Morris,
S. Silverman,
T. Trenti,
D. A. Wahl,
C. Cooper,
J. A. Kanis,
for the IOF-IFCC Bone Marker Standards Working Group
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ABSTRACT: SummaryThe International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine
(IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption
(serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical
studies.
IntroductionBone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial
proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction
of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda.
MethodsEvidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and
2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001.
ResultsHigh levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been
used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base
practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely
used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation
of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control.
IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers
and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives
and to enlarge the international experience of the application of markers to clinical medicine.
ConclusionBTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in
part resolved by adopting international reference standards.
KeywordsBone makers–Bone turnover–Fracture risk–IOF–Monitoring treatment–Reference standards
Osteoporosis International 04/2012; 22(2):391-420. · 4.58 Impact Factor
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O Bruyère,
B Avouac,
P Richette,
E Maheu,
P Bruel,
V Coxam,
G B Guillou,
A-E Lugrin,
C Merceron,
T Pauquai,
F Rannou,
P Ythier-Moury,
Y Tsouderos,
N Urban,
L Rovati,
J Guicheux,
J-Y Reginster
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ABSTRACT: In 2006, the European Parliament and Council issued a regulation (No. 1924/2006) for the nutrition and health claims made on foods, including food supplements. According to the regulation, the use of nutrition and health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect. In the field of joint and cartilage health, there is no clear scientific-based definition of the nature of such a beneficial nutritional or physiological effect. The objective of this paper is to scientifically define the possible content of health claims related to joint and cartilage health and to provide scientific guidelines for the design of clinical studies which need to be adopted to substantiate such health claims.
Literature review up to September 2011 followed by a consensus expert discussion organized by the Group for the Respect of Ethics and Excellence in Science (GREES).
In line with the general principles of the PASSCLAIM and the Codex recommendations, the GREES identified four acceptable health claims related to joint and cartilage health based on the effects on discomfort, joint and cartilage structural integrity or risk factors for joint and cartilage diseases. The GREES considers that randomized controlled trials on a relevant outcome is the best design to assess health claims. Moreover, animal studies could also be of interest to substantiate some health claims, to assess the clinical relevance of endpoints used in human studies or to extrapolate data obtained in patients to the target (apparently) healthy population.
According to the methodology and biomarkers used in the study and whether or not additional animal studies are provided to support the claim, various health claims can be acceptable in the field of joint and cartilage health.
Current Medical Research and Opinion 03/2012; 28(4):611-6. · 2.38 Impact Factor
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J-Y Reginster,
J-M Kaufman,
S Goemaere,
J P Devogelaer,
C L Benhamou,
D Felsenberg,
M Diaz-Curiel,
M-L Brandi,
J Badurski,
J Wark,
A Balogh, O Bruyère,
C Roux
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ABSTRACT: In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term.
Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years.
Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm.
The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years.
Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate.
Osteoporosis International 11/2011; 23(3):1115-22. · 4.58 Impact Factor
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S Vasikaran,
R Eastell, O Bruyère,
A J Foldes,
P Garnero,
A Griesmacher,
M McClung,
H A Morris,
S Silverman,
T Trenti,
D A Wahl,
C Cooper,
J A Kanis
[show abstract]
[hide abstract]
ABSTRACT: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical studies.
Bone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda.
Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001.
High levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control. IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine.
BTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.
Osteoporosis International 02/2011; 22(2):391-420. · 4.58 Impact Factor
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ABSTRACT: Health claims for food products in Europe are permitted if the nutrient has been shown to have a beneficial nutritional or physiological effect. This paper defines health claims related to bone health and provides guidelines for the design and the methodology of clinical studies to support claims.
Regulation (EC) no. 1924/2006 on nutrition and health claims targeting food products was introduced in Europe stating that health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect. The objective of this paper is to define health claims related to bone health and to provide guidelines for the design and the methodology of clinical studies which need to be adopted to assert such health claims.
Literature review followed by a consensus discussion during two 1-day meetings organized by the Group for the Respect of Ethics and Excellence in Science (GREES).
The GREES identified six acceptable health claims related to bone health based on the potential of food products to show an effect on either the bioavailability of calcium or osteoclast regulatory proteins or bone turnover markers or bone mineral density or bone structure or fracture incidence. The GREES considers that well-designed human randomized controlled trial on a relevant outcome is the best design to assess health claims. The substantiation of health claim could also be supported by animal studies showing either an improvement in bone strength with the food product or showing the relationship between changes induced by the food product on a surrogate marker and changes in bone strength.
The consensus reached is that the level of health claim may differ according to the surrogate endpoint used and on additional animal studies provided to support the claim.
Osteoporosis International 02/2011; 23(1):193-9. · 4.58 Impact Factor
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ABSTRACT: Surrogate measures of fracture risk, such as effects on bone mineral density, may be of great interest to assess the efficacy of available osteoporosis treatments.Our results suggest that bone mineral density (BMD)changes cannot be used as a surrogate of anti-fracture efficacy, among patients receiving calcium, with or without vitamin D.
The purpose of this study is to examine the association between changes in bone mineral density with reduction in the risk of fractures in patients receiving calcium with or without vitamin D.
We selected all randomized placebo-controlled clinical trials of calcium with or without vitamin D supplementation. To be included in this analysis, the studies were required to report both BMD (hip/proximal femur and/or lumbar spine) and the incidence of fractures. Meta-regression analyses were used to examine the associations of changes in BMD with reduction in risk of fracture over the duration of each study. The change in BMD was the difference between changes (from baseline) observed in the active treatment group and placebo group.
A total of 15 randomized trials (n=47,365) were identified, most of whom (77%) came from the Women's Health Initiative trial. Results show that larger increases in BMD at the lumbar spine were not associated with greater reduction in fracture risk. Concerning hip BMD changes,we found a statistically significant relationship between hip BMD changes and reduction in risk. However, results were not quite significant after excluding the both largest studies, in which BMD changes were measured in very small subset of patients. These points may have largely biased our results.
In conclusion, there was no evidence of a relationship between BMD changes and reduction in risk of fractures among patients receiving calcium with or without vitamin D supplementation. Calcium and/or Vitamin D may reduce fracture rates through a mechanism independent of bone density.
Osteoporosis International 11/2010; 22(3):893-901. · 4.58 Impact Factor
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ABSTRACT: The aim of this study was to explore the cost-effectiveness of glucosamine sulphate (GS) compared with paracetamol and placebo (PBO) in the treatment of knee osteoarthritis. For this purpose, a 6-month time horizon and a health care perspective was used.
The cost and effectiveness data were derived from Western Ontario and McMaster Universities Osteoarthritis Index data of the Glucosamine Unum In Die (once-a-day) Efficacy trial study by Herrero-Beaumont et al. Clinical effectiveness was converted into utility scores to allow for the computation of cost per quality-adjusted life year (QALY) For the three treatment arms Incremental Cost-Effectiveness Ratio were calculated and statistical uncertainty was explored using a bootstrap simulation.
In terms of mean utility score at baseline, 3 and 6 months, no statistically significant difference was observed between the three groups. When considering the mean utility score changes from baseline to 3 and 6 months, no difference was observed in the first case but there was a statistically significant difference from baseline to 6 months with a p-value of 0.047. When comparing GS with paracetamol, the mean baseline incremental cost-effectiveness ratio (ICER) was dominant and the mean ICER after bootstrapping was -1376 euro/QALY indicating dominance (with 79% probability). When comparing GS with PBO, the mean baseline and after bootstrapping ICER were 3617.47 and 4285 euro/QALY, respectively.
The results of the present cost-effectiveness analysis suggested that GS is a highly cost-effective therapy alternative compared with paracetamol and PBO to treat patients diagnosed with primary knee OA.
International Journal of Clinical Practice 05/2010; 64(6):756-62. · 2.41 Impact Factor
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ABSTRACT: The objective of this study was to evaluate a Belgian version of the WHO fracture risk assessment (FRAX) tool to compute 10-year probabilities of osteoporotic fracture in men and women. A particular aim was to determine fracture probabilities that corresponded to the reimbursement policy for the management of osteoporosis in Belgium and the clinical scenarios that gave equivalent fracture probabilities. Fracture probabilities were computed from published data on the fracture and death hazards in Belgium. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck BMD. Fracture probabilities were determined that were equivalent to intervention (reimbursement) thresholds currently used in Belgium. Fracture probability increased with age, lower BMI, decreasing BMD T-Score, and all clinical risk factors used alone or combined. The FRAX tool has been used to identify possible thresholds for therapeutic intervention in Belgium, based on equivalence of risk with current guidelines. The FRAX model supports a shift from the current DXA based intervention strategy, towards a strategy based on fracture probability of a major osteoporotic fracture that in turn may improve identification of patients at increased fracture risk. The approach will need to be supported by health economic analyses.
Revue médicale de Liège 12/2009; 64(12):612-9.
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ABSTRACT: The first objective was to assess the effect of the chondroitin 4 and 6 sulphate (CS) on health-related quality of life using utility values in patients with knee osteoarthritis (OA) during a 24-month treatment course. The second objective was, using these data, to conduct economic analyses.
Data from the STOPP study was used. This study was a randomised, double-blind, placebo (PL) -controlled trial of 2-year duration. In the STOPP study, authors assessed quality of life using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). WOMAC scores were translated into Health Utility Index (HUI) scores using a specific formula. Incremental cost effectiveness ratio (ICER) was calculated taking into account the cost of CS and its effect on HUI scores, compared to PL.
At baseline, the mean (SD) HUI scores were 0.59 (0.17), and 0.59 (0.18) for the PL and CS groups, respectively (p=0.31 between the two groups). The mean (SD) HUI scores changes from baseline to 6 months were 0.02 (0.02), and 0.05 (0.01) for the PL and CS groups, respectively (p=0.03). After 24 months of follow-up, HUI score increases by 0.04 (0.02) in the PL group and by 0.05 (0.02) in the CS group (p=0.37). Using the price bracket of CS in Europe, ICER assessment always resulted in a cost below €30,000 per QALY gained, after 6, 12 and 24 months of treatment.
CS treatment increases health utilities in patients with knee OA compared to PL over the first 6 months of treatment. Economic evaluation based on these data suggests that CS treatment could be considered as cost-effective in patients with knee OA up to a period of 24 months. A limitation in this study is the absence of direct utility assessment as well as the absence of effective treatment as comparator.
Journal of Medical Economics 11/2009; 12(4):356-60.
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ABSTRACT: From two randomised controlled trials, it is shown that 3-month changes in biochemical markers of bone formation (bone-specific alkaline phosphatase and C-terminal propeptide of type I procollagen) were associated with 3-year bone mineral density (BMD) changes, but not fracture incidence in patients treated with strontium ranelate.
The purpose of this study was to assess if short-term change in biochemical markers of bone remodelling is associated with long-term BMD change and fracture incidence observed during treatment with strontium ranelate.
From the SOTI and TROPOS trials, bone-specific alkaline phosphatase (BALP), C-terminal propeptide of type I procollagen (PICP), serum C-terminal telopeptides (S-CTX) and urine N-terminal telopeptides of type I collagen (U-NTX) were assessed at baseline and after 3 months.
Two thousand three hundred seventy-three women were included in this study. Multiple regression analysis showed that 3-month changes in PICP and BALP but not s-CTX I nor s-NTX I were significantly (p < 0.001) associated with 3-year BMD changes at the lumbar spine and the femoral neck. Changes in s-CTX I, PICP and BALP were significantly associated with change in total proximal femur BMD. Changes in biochemical markers explain less than 8% of the BMD changes. The 3-month changes in BALP, PICP s-CTX I and s-NTX I were not significantly associated with fracture incidence.
Short-term changes in biochemical markers of bone formation are associated with future BMD changes in patients treated with strontium ranelate, suggesting a bone-forming activity of this treatment, but are not appropriate to monitor the efficacy of strontium ranelate at the individual level.
Osteoporosis International 10/2009; 21(6):1031-6. · 4.58 Impact Factor
