Assessment of health claims in the field of bone: a view of the Group for the Respect of Ethics and Excellence in Science (GREES).

UNLABELLED: 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. INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Primary osteoarthritis of hip, knee, and hand in relation to occupational exposure.

AIM: To identify occupations with excess prevalence of osteoarthritis of the knee, hip, and hand in a nationwide survey and to compare occupations with and without excess prevalence with regard to biomechanical stresses and severity of osteoarthritis. METHODS: Patients presenting with osteoarthritis of the knee, hip, or hand were recruited throughout France by their treating physician who collected information on history, including age at onset, occupation, and occupational stresses to joints. Severity was assessed using joint specific functional status questionnaires: Lequesne for the hip and knee and Dreiser for the hand. The distribution of osteoarthritis patients by occupation was compared with the distribution of occupations in all workers in France to obtain prevalence rate ratios. RESULTS: Occupations with the greatest prevalence rate ratio were female cleaners (6.2; 95% CI 4.6 to 8.0), women in the clothing industry (5.0; 95% CI 3.9 to 6.3), male masons and other construction workers (2.9; 95% CI 2.6 to 3.3), and agriculture male and female workers (2.8; 95% CI 2.5 to 3.2). A twofold greater prevalence rate was observed within certain occupations between self-employed and salaried workers. Early onset of osteoarthritis was seen in the more heavy labour jobs with almost 40% of patients reporting their first symptoms before the age of 50. CONCLUSION: The early onset and severity of osteoarthritis in certain occupations warrants an urgent need for occupation specific studies for the development and evaluation of preventive strategies in this leading cause of disability in Western countries.

Ketoprofen: the European experience.

An overview of European experience with ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) with analgesic properties, from the time of its marketing in 1973 until the present is presented. Orally administered ketoprofen (200 mg/day) has been proven effective in treating rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Furthermore, several alternate dosage forms, including intramuscular injection for relief of acutely painful conditions, suppositories, two slow-release forms (a sustained-release tablet [IBP 200] and a controlled-release capsule [Oruvail] ), and a topical gel for local treatment of certain superficial conditions and minor rheumatologic disease are available. The safety of ketoprofen has also been proven in several European postmarketing surveillance studies and more importantly, by French and British drug monitoring data. Ketoprofen was rated as one of the safest NSAIDs available in the United Kingdom (UK) by the Committee on the Safety of Medicine in 1986. For incidence of gastrointestinal complaints per million prescriptions, ketoprofen ranked seventh among 19 NSAIDs in its first five years of marketing in the UK. Ketoprofen has been associated with a very low incidence of serious renal, hepatic, or cutaneous reactions. Thus ketoprofen, in 15 years of marketed use in Europe, has proven to be an effective anti-inflammatory and analgesic agent with an excellent safety profile and several convenient dosage forms.

Guidelines for clinical studies assessing the efficacy of drugs for the management of acute low back pain.

In this paper we propose guidelines for clinical trials aimed at assessing the efficacy of drugs for acute non-specific low back pain (LBP) with or without radicular pain, preliminary to their approval and registration. To this end, consensus statements were obtained from a group of experts in the fields of rheumatology, clinical medicine, public health and epidemiology. EBM resources were systematically used as references. Four diagnostic categories were defined: type 1--LBP with no radiation; type 2--LBP radiating no further than the knee; type 3--LBP radiating beyond the knee, but with no neurologic signs; and type 4--LBP radiating to a specific and entire leg dermatome, with or without neurologic signs. Studies should be designed on the basis of the claimed indications for the drug, but must be double-blinded whatever the indication. The duration of the study may be shorter for LBP type 1 or 2 (one week) than for LBP types 3 and 4 (up to one month), depending on the aim of the study and the indications for the drug. The comparator may be inactive (placebo) or active (for a superiority trial, e.g., versus paracetamol). Specific inclusion and exclusion criteria have been defined here for each category. An appropriate wash-out period for any drugs that could affect the pain status should be planned. Paracetamol may be allowed as rescue medication. The primary endpoint should be based on a validated pain assessment tool that may be either generic (type 1 or 2) or oriented (back and knee for types 3 and 4). Secondary endpoints could include the assessment of functional performance; the duration of any period of bed-rest; work limitation; a global assessment comprising pain at rest, standing and walking; the time elapsed before epidural injection, the prescription of other therapeutic agents, or surgery; and the use of rescue medication. Adverse events (AE) should be monitored systematically using a methodology that reflects the mode of action of the tested drug. With the application of these guidelines, LBP could serve as an appropriate disease for testing analgesic drugs. Rigorous evaluation may also help to improve the management of acute LBP.

Primary osteoarthritis and occupations: a national cross sectional survey of 10 412 symptomatic patients.

AIMS: To describe the age standardised prevalence of symptomatic osteoarthritis (OA) in a nationwide cross sectional survey of 10 412 patients in France, and their functional and work limitations. METHODS: Cases in the survey were compared with their expected counterpart by age, gender, and occupational groupings using data from the 1998 French National Survey on Health Impairment and Disability. RESULTS: Women represented 66.2% of the sample; mean age was 66.2 years. One third of patients had OA of the knee, 16% of the hip, and 12% of the hand; a third had multiple joint OA. Peak prevalence of symptomatic OA was in the 60-69 year category in women and in the 70-79 year category in men. Agricultural workers showed a significant excess prevalence of OA, with an observed to expected (O/E) ratio of 1.7 in women and 2.3 in men. Linear trends in prevalences between white collar, "mixed" collar, and blue collar workers were also significant, with odds ratios respectively of 1.0, 2.9, and 2.6 in women and 1.0, 1.2, and 1.7 in men. Specific excess prevalence was found in women among housekeepers (O/E 4.4), and in men among unskilled labour workers (O/E 10.3) and truck drivers (O/E 6.7). Total work disability was highest among blue collar workers and partial disability among agricultural workers. CONCLUSION: Results contribute to the mounting evidence that OA is potentially aetiologically linked to occupation in a sizeable segment of the population and that OA can no longer be considered an inevitable disease of ageing.

[Evaluation of the medical value of a drug. A necessity for the Transparency Commission]. / L'évaluation du service médical rendu. Une nécessité pour la Commission de la Transparence.

The marketing approval (AMM) is based on criteria of pharmaceutical quality, efficacy and safety of use. Before marketing, the data are collected by means of double-blind, randomized, prospective clinical trials that compare the study product to a reference product. A post-AMM assessment is needed to define the increase of the medical benefit (ASMR) and the therapeutic value of the new drugs. The quantification of the ASMR is essential for registration on the list of drugs reimbursable for those who benefit from Social Security. The evaluation of the therapeutic value and the nature of the affection treated are the criteria upon which the reimbursement ratio is chosen. After marketing, the reevaluation of the medical benefit and the drugs' usefulness may be compared to the treatment's net medical cost (direct + indirect cost--avoided cost) in cost/utility or cost/benefit studies. The Transparency Commission has worked out a scale of assessment of the ASMR which will orient recommendation, or non-recommendation, of registration on the list of reimbursable drugs as well as price fixing proposals. In the future, the Transparency Commission is to strengthen its position regarding the good use of the drug through a better prescriber information system. Thanks to the pharmaco-epidemiology and the pharmaco-vigilance data, the Transparency Commission will be able to guarantee the post-marketing follow-up of the drugs. The examination of the products' conditions of use, the reevaluation of the treatment's advantages based on the utility studies and the epidemiological surveys, and the cost-benefit studies will contribute to a medical control of health spending linked to drug consumption.

[Role of radiology in the diagnosis of joint chondrocalcinosis. Calcium pseudogout]. / La place de la radiologie dans le diagnostic de la chondrocalcinose articulaire. La pseudo-goutte calcique.

Chondrocalcinosis is a really frequent clinicopathologic entity, which is caused by the penetration of calcium pyrophosphate dihydrate microcrystals into the structures of the joint, including hyaline cartilages and fibrocartilages--hense its name--as well as the synovial fluid and membrane. Calcium gout, which preferentially appears in the knees, is the most spectacular and characteristic symptom of chondrocalcinosis, expressing a crisis of acute microcrystal synovitis, of which it has all the usual clinical features, and thus simulating uratic gout. The positive diagnosis is based on: a) the radiologic demonstration of articular calcifications in the lining cartilages, forming a continuous or fragmented opaque border on the subchondral bone, from which it is separated by a light space, and/or in the fibrocartilaginous structures (most often the menisci, the symphysis pubis, the disk of the inferior radioulnar joint) where they appear as small, irregular clusters with blurred or cloudy margins. The knee is the most frequent site of calcium impregnation images, both in hyaline cartilages and in fibrocartilages. b) the presence of calcium pyrophosphate microcrystals in the synovial fluid; their nature is usually demonstrated convincingly enough with a conventional light microscope; c) needle biopsy findings of microcrystalline clusters embedded in the synovial membrane, that can be easily identified with routine staining. In practice, demonstrating radiologic signs, when these are characteristic and can be detected in their preferred sites, allows recognizing diffuse chondrocalcinosis in satisfactory safety conditions after a calcium gout crisis, as well as in the presence of the many atypical or misleading symptomatic aspects of this microcystal arthropathy, that will be the subject of a further paper.

[Role of radiology in the diagnosis of joint chondrocalcinosis. The so-called atypical symptomatic aspects]. / La place de la radiologie dans le diagnostic de la chondrocalcinose articulaire. Les aspects symptomatiques dits atypiques.

In a preceding article, we described "pseudogout" which is the expression of an episode of acute synovitis related to microcrystals of dehydrated calcium pyrophosphate invading the joint. This brutal episode of inflammation, predominantly occurring in the knee joint, is the most spectacular, most frequent and most characteristic manifestation of articular chondrocalcinosis. We attempted to demonstrate the important role of radiographs in the diagnosis, discovering in many cases the microcrystal impregnation of cartilage and fibrocartilage. But articular chondrocalcinosis, as has been shown by a large number of clinical and radiological surveys, may present a wide range of atypical or misleading forms, much different from the classic pseudogout. Among the different clinical presentations, some have no particularly special radiographic expression, showing only the common chondrocalcinosis lesions seen during the acute episodes of microcrystal related synovitis. This is the case in different situations of inflammation, notably subacute arthritis, purely algic forms and exsudative forms (chronic hydarthrosis, haemarthrosis). Complete clinical latency is also observed in certain cases. But many cases of articular chondrocalcinosis involve manifest radiological lesions which often appear to be secondary. This may occur in chronic inflammatory forms of chondrocalcinosis which can simulate rheumatoid polyarthritis. Careful analysis of the symptomatology should help to avoid confusion, especially when the radiograph reveals only degenerative lesions which often cause destructive damages. In other cases, a perfectly characteristic articular chondrocalcinosis is associated with typical polyarticular lesions of osteoarthritis. These cases often have the particularity of involving joints usually spared by the common arthrosic disease, especially in the upper limbs. They are also remarkable due to the amount of lytic damage. The deep destructive damage to joints during chondrocalcinosis may produced a particularly striking picture. Such damage is seen in approximately one-third of the cases. The onset is marked by sudden renewal of former arthrosic-type pain and by the development of major functional incapacity. Often, the radiograph is the only examination capable of revealing the diagnosis. The extent of bone destruction varies greatly. Sometimes it is limited to subchondral bone but in other cases underlying bony structures are also involved leading to extensive damage to the epiphysis. The distribution of lytic lesions varies. Damage may occur in the knee, the coxofemoral and the shoulder joints. Surgery is often absolutely indicated. In a number of cases of chondrocalcinosis, especially those involving the knee and the shoulder, true intraarticular foreign bodies may be encountered, opaque calcified or ossified formations simulating osteochondromatosis, existing along with destructive damages.(ABSTRACT TRUNCATED AT 400 WORDS)

[Current medical possibilities in the treatment of arthrosis]. / Possibilités thérapeutiques médicales actuelles de l'arthrose.

DRUG CLASSES: Three drug classes can be distinguished. The first includes drugs used for symptomatic care. This class includes a subclass of rapid action drugs (antalgesics, nonsteroidal antiinflammatory drugs, NSAID) and a subclass of symptomatic slow acting drugs. The second class corresponds to antiosteoartritis drugs called chondroprotective drugs or structure modifying. The third class includes drugs used for local care. TREATMENT STRATEGY: For episodes of acute pain, the first intention prescription should include rapid action drugs for symptomatic relief (paracetamol then NSAID). A symptomatic slow acting antiosteoarthritis drug can also be associated then continued after interrupting the rapid action symptomatic drugs. Diacerein is a drug with prolonged antiosteoarthritis action that has proven efficacy for symptom relief equi-valent to NSAID assessed in terms of pain relief and function: the ECHODIAH study provides arguments favoring its chondromodulating effect.

Health claims assessment in the field of joint and cartilage: a consensus viewpoint of the Group for the Respect of Ethics and Excellence in Science.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.