Crizotinib-induced osteitis mimicking bone metastasis in a stage IV ALK-rearranged NSCLC patient: a case report.

BACKGROUND: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. CASE PRESENTATION: A 31-year-old woman with stage IV ALK-rearranged NSCLC presented with back pain after 3 months of crizotinib treatment. Diagnostic work-up showed osteitis on the 4th and 5th thoracic vertebrae, anterior soft tissue infiltration and epiduritis, without any sign of infection. Spinal cord decompression, histological removal and osteosynthesis were performed. Histologic examination showed necrosis with abundant peripheral neutrophils, no microorganism nor malignant cell. Symptoms and Computarized Tomography-abnormalities rapidly diseappeared after crizotinib withdrawal and did not recur after ceritinib onset. CONCLUSIONS: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression.

Usefulness of monitoring of B cell depletion in rituximab-treated rheumatoid arthritis patients in order to predict clinical relapse: a prospective observational study.

Our objective was to evaluate the contribution of monitoring B cell subset depletion after rituximab in patients with rheumatoid arthritis (RA) in order to guide reintroduction to forestall relapse. This prospective, monocentre study included all RA patients receiving two 1-g rituximab infusions at a 15-day interval. The patients were followed clinically and biologically every 2 months until rituximab reintroduction. The physician was blinded to lymphocyte-typing results to diagnose relapse and, hence, retreatment. Among the 39 patients included between March 2010 and December 2011 and followed until April 2013, seven received two rituximab cycles, yielding a total of 46 cycles for analysis. After the two rituximab cycles, the total number of CD19(+) B cells decreased significantly (0·155 versus 0·0002 G/l, P < 0·0001), with complete depletions in all patients of CD19(+) CD38(++) CD24(++) (transitional) (P < 0·0001) and CD19(+) CD27(+) (memory) B lymphocytes. A significant majority of patients relapsed within the 4 months following repopulation of total B (P = 0·036), B transitional (P = 0·007) and B memory (P = 0·01) lymphocytes. CD19(+) B lymphocyte repopulation preceded clinical RA relapse and enabled its prediction 4 months in advance. Hence, monitoring of CD19(+) B lymphocytes could serve as a tool to predict those relapses.

The impact of an in-department pharmacist on the prevention of drug iatrogenesis in a rheumatology department.

INTRODUCTION/OBJECTIVES: The primary objective was to evaluate the impact of an in-department pharmacist on the prevention of drug iatrogenesis in a rheumatology department. Secondary objectives were to determine (i) if medication history discrepancies were detected more frequently in the elderly or not, and (ii) if the mean number of treatments at admission had an impact on the number of medication history discrepancies. METHODS: Implementation of a clinical-pharmacy program based on medication reconciliation and medication review of prescription for all patients admitted to a rheumatology department between January and June 2017. The analytical approach was mainly descriptive and data were expressed as mean ± standard deviation (i.e., number of treatments at admission, number of medication reconciliations) and as proportions (i.e., acceptance rate, impact). Chi-squared tests and Student's test were performed to determine if there was a significant difference in outcomes. RESULTS: Three hundred twelve patients were included in the study, 517 medication history discrepancies in 243 (77.8%) patients and 196 pharmaceutical interventions in 133 (42.6%) patients. A significant difference was found in the number of medication history discrepancies and pharmaceutical interventions between the two age groups and in the mean number of treatments at admission between patients with or without medication history discrepancies. 15.4% of study patients had major medication history discrepancies and major pharmaceutical interventions. All patients and practitioners reported the usefulness of an in-department pharmacist. CONCLUSION: This program was found effective in terms of safety and improvement in the continuity of care. Key Points • This clinical-pharmacy program with an in-department pharmacist had a positive impact on the prevention of drug iatrogenesis in one rheumatology department. • 15.4% (n = 48) of study patients had major medication history discrepancies and major pharmaceutical interventions. • All practitioners and patients were satisfied with this clinical-pharmacy program.

Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anti-citrullinated protein antibodies to very early rheumatoid arthritis diagnosis.

OBJECTIVES: To evaluate the predictive value of TNFRII 196R, PTPN22 1858T and HLA-shared epitope (SE) alleles, RFs and anti-citrullinated protein antibodies (ACPAs) for RA diagnosis in a cohort of patients with very early arthritis. METHODS: We followed up 284 patients who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for <6 months. At 2 yrs, patients were classified as having RA or non-RA rheumatic diseases according to the ACR criteria. Patients were genotyped with respect to TNFRII 196M/R and PTPN22 1858C/T polymorphisms and HLA-SE. The presence of IgA, IgG and IgM RF isotypes and ACPA was sought in sera collected at disease onset. RESULTS: HLA-SE alleles alone, concomitant presence of TNFRII 196R and PTPN22 1858T alleles, IgA, IgG and IgM RF alone and ACPA were found to be significantly associated with RA diagnosis. Using logistic regression analysis, the concomitant presence of RF and ACPA at disease onset was the best association to predict RA diagnosis. In patients (n = 34) who did not fulfil the ACR criteria for RA at inclusion but who progressed to ACR positivity, the study of the genetic risk markers did not contribute to predict RA diagnosis at 2 yrs. CONCLUSIONS: PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the predictive value of RF and ACPA for RA diagnosis in our cohort, and do not contribute to an earlier diagnosis in undifferentiated patients initially negative for RF and ACPA.

Pre-silencing of genes involved in the electron transport chain (ETC) pathway is associated with responsiveness to abatacept in rheumatoid arthritis.

BACKGROUND: In the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA. METHODS: Whole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA. Data validation by quantitative reverse-transcription (qRT)-PCR was performed from a second independent subset of 32 patients with RA. Gene Ontology and WikiPathways database allowed us to highlight the specific biological mechanisms involved in predicting response to ABA/MTX. RESULTS: From the first subset of 36 patients with RA, a combination including 87 transcripts allowed almost perfect separation between responders and non-responders to ABA/MTX. Next, the second subset of patients 32 with RA allowed validation by qRT-PCR of a minimal signature with only four genes. This latter signature categorized 81% of patients with RA with 75% sensitivity, 85% specificity and 85% negative predictive value. This combination showed a significant enrichment of genes involved in electron transport chain (ETC) pathways. Seven transcripts from ETC pathways (NDUFA6, NDUFA4, UQCRQ, ATP5J, COX7A2, COX7B, COX6A1) were significantly downregulated in responders versus non-responders to ABA/MTX. Moreover, dysregulation of these genes was independent of inflammation and was specific to ABA response. CONCLUSION: Pre-silencing of ETC genes is associated with future response to ABA/MTX and might be a crucial key to susceptibility to ABA response.

Long term outcome of patients with low level of cryoglobulin (<0.05g/L).

OBJECTIVES: To date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (≤0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin ≤0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level ≤0.05 g/L and those exhibiting cryoglobulin level >0.05 g/L. METHODS: Among 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed. RESULTS: Of the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level ≤0.05 g/L. We showed that patients with cryoglobulin level ≤0.05 g/L had: 1) less commonly: palpable purpura (p<0.001), digital ulcers (p=0.006), peripheral neurologic involvement (p=0.03) and renal impairment (p=0.03); and 2) lower median values of ESR (p<0.001) and C-reactive protein (p=0.001). The patients with cryoglobulin level ≤0.05 g/L less often experienced infections (p=0.04) and hematological malignancies (p=0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level ≤0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%). CONCLUSION: Our study shows a high prevalence of cryoglobulin level ≤0.05 g/L in clinical practice. Our findings further underscore that non-HCV cryoglobulin level ≤0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow-up may be required to improve such patients' outcome.

Association between RANK, RANKL and OPG polymorphisms with ACPA and erosions in rheumatoid arthritis: results from a meta-analysis involving three French cohorts.

OBJECTIVES: The RANK/RANKL/osteoprotegerin (OPG) system plays a central role in the pathogenesis of bone erosions in rheumatoid arthritis (RA). The aim of this study was to test the association between 11 single-nucleotide polymorphisms (SNPs) located on RANK, RANKL and OPG genes and anticitrullinated peptide antibody (ACPA) presence or erosions in RA. PATIENTS: This work was performed on three independent samples of French patients with RA: the Etude de Suivi des PolyArthrites Indifférenciées Récentes (ESPOIR) (n=632), Rangueil Midi-Pyrénées (RMP) (n=249) and French Rheumatoid Arthritis Genetic Consortium (FRAGC) (n=590) cohorts. Genotyping: the genotyping of 11 SNPs located on RANK, RANKL and OPG were performed by PCR. STATISTICAL ANALYSES: The association between the genotypes with ACPA or erosions was first tested in the ESPOIR cohort using a χ(2) test and, in the case of significant association, replicated in the RMP and FRACG cohorts. A meta-analysis on the three cohorts was performed using the Mantel-Haenszel method. RESULTS: One SNP on RANK (rs8086340) and three SNPs on RANKL (rs7984870, rs7325635, rs1054016) were significantly associated with ACPA presence, while one SNP on OPG (rs2073618) and one SNP on RANKL (rs7325635) were significantly associated with erosions in the ESPOIR cohort. Following meta-analysis performed on the three samples, the SNP on RANK and the GGG haplotype of the three SNPs located on RANKL were both significantly associated with ACPA presence, while only the SNP on OPG remained significantly associated with erosions. CONCLUSIONS: This study identified one SNP located on RANK, one haplotype on RANKL associated with ACPA presence, and one SNP located on OPG associated with erosions in three different samples of French patients with RA.

Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome.

OBJECTIVE: To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). METHODS: A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. RESULTS: One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. CONCLUSION: In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.

[Psoriatic arthritis during rituximab treatment of granulomatosis with polyangiitis: a new paradoxical side effect?]. / Rhumatisme psoriasique au cours d'un traitement par rituximab pour une polyangéïte avec granulomatose : une nouvelle réaction paradoxale ?

INTRODUCTION: Rituximab is a monoclonal antibody targeting the CD20 molecule of the B lymphocyte. Its efficacy has been recently reported in ANCA-associated vasculitis. We report a case of psoriatic arthritis that occurs during a treatment with rituximab in granulomatosis with polyangiitis. CASE REPORT: A 66-year-old woman, without past history of psoriasis, presented with a relapsing granulomatosis with polyangiitis in July 2010 with sinus and lung involvement. Treatment with rituximab was started, allowing a complete remission in 6 months. Two months after the first two infusions of rituximab she developed asymmetric arthritis of 3 distal interphalangeal joints. A few months later, the clinical presentation showed asymmetrical arthritis of the hands and wrists and dactylitis. Standard radiographs and MRI showed an inflammatory impairment according with psoriatic arthritis. CONCLUSION: Accountability of rituximab was retained in the development of the disease given the chronology of psoriatic arthritis development. It may be a paradoxical reaction, by analogy to those observed in anti-TNFα.

Spinal abscess and spondylitis due to actinomycosis.

STUDY DESIGN: Report of a rare case of spinal actinomycosis in a young immunocompetent woman. OBJECTIVE: To show the difficulties in diagnosing spinal actinomycosis. SUMMARY OF BACKGROUND DATA: Spinal actinomycosis is rare and usually occurs as a result of a contiguous (abdominal, pelvic, or thoracic) spread of the infection. This localization represents less than 5% of the infectious sites and was mainly, before the penicillin era, a postmortem discovery. METHODS: A case is reported of a 34-year-old Algerian woman who had fever, persistent cough, right-side thoracic pain, and progressive severe back pain. Radiographs, computed tomographic scan, and magnetic resonance imaging demonstrated lytic areas on the vertebral bodies of T11 and T12 and a paravertebral mass, without disk involvement. A surgical biopsy of T12 and the paravertebral abscess was performed. RESULTS: Presence of characteristic sulfur granules and gram-positive filamentous bacteria in surgical biopsy tissues and isolation of Actinobacillus actinomycetemcomitans in cultures led to the diagnosis of vertebral actinomycosis. The patient was virtually free of pain and fever after a 3-month regimen of ofloxacin and rifampicin (Rifadine, Marion-Merell, France) and was without recurrence after 18 months of follow-up. CONCLUSIONS: Actinomycosis of the spine, caused by the spread of a paraspinal abscess, is extremely rare. The previously poor prognosis has been transformed by antibiotics.

Anti-TNF-alpha-induced systemic lupus syndrome.

Anti-TNF-alpha therapies are promising new strategies in the treatment of rheumatoid arthritis (RA). Despite good clinical efficacy and tolerance, the possible occurrence of drug-induced autoimmune disorders remains a matter of concern. Induction of antinuclear (ANA) and anti-DNA antibodies is observed in some patients treated with TNF-alpha inhibitors (anti- TNF-alpha antibodies) or soluble TNF-alpha receptor. Of concern is the possibility of induction of true lupus erythematosus by TNF blockers. Few cases without major organ involvement were reported to be associated with infliximab treatment that resolved after anti-TNF discontinuation. Only four cases have been described with the use of etanercept. We report a new case of infliximab-induced lupus syndrome and two new cases of etanercept-induced lupus syndrome in three patients with RA, all of whom had previous isolated positive ANA.

Antibodies and vascular involvement in inflammatory joint disease: clinical relevance.

The vascular endothelium is a common target of inflammatory joint disease. Autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome can be responsible for a spectrum of vascular disorders that encompasses vasculitis, thrombosis and/or atheroma associated with the antiphospholipid syndrome, and vascular damage caused by cryoglobulin deposition. These mechanisms can coexist, particularly in lupus patients. Joint disease is sometimes the presenting manifestation in primary vasculitis. Autoantibodies are detectable in most patients with vascular involvement and inflammatory joint disease. They are not merely markers for vascular involvement: in vitro and in vivo data suggest that some autoantibodies may contribute to the genesis of endothelial lesions, together with other factors. For instance, evidence of pathogenic effects has been found for antineutrophil cytoplasmic antibody (ANCA), most notably with antimyeloperoxidase or antiproteinase-3 specificity, in small-vessel vasculitides (Wegener's granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis); for immune complexes, particularly those containing cryoglobulins, in vasculitides secondary to CTDs; and for circulating anticoagulant and anticardiolipin antibodies, above all anti-beta2-glycoprotein I, in antiphospholipid syndrome. Antibodies to annexin V, modified lipoproteins, and endothelial cells may be of interest; their clinical relevance is unclear, however, and no standardized assays are available, so thatthese antibodies are not looked for in everyday practice. When deciding which antibody tests should be performed in a given patient, the circumstances surrounding the onset of the vasculopathy should be borne in mind. In patients with previous CTD, the tests are selected based on the diagnosis. In contrast, in a patient with no previous diagnosis, a vasculopathy can be either primary or secondary to undiagnosed CTD or to antiphospholipid syndrome: consequently, a broader array of tests is needed in this situation.

A shock associated with adult-onset Still's disease.

Only two cases of adult-onset Still's disease associated with shock have been previously described. We report a case of shock in a man with adult-onset Still's disease and discuss the relationship between the two processes by assessing tumor necrosis factor-alpha, procalcitonin and interleukin-6 concentrations.

Prospective X-ray densitometry and ultrasonography study of the hand bones of patients with rheumatoid arthritis of recent onset.

OBJECTIVE: Bone demineralization observed in early rheumatoid arthritis is not easily measured. To measure bone loss and to discriminate between rheumatoid arthritis and other rheumatic diseases, we used two methods: dual-energy X-ray absorptiometry and ultrasonography. METHODS: From a population-based recruitment, 32 patients with early peripheral polyarthritis (median disease duration: 4 months) were studied. Clinical, laboratory, functional, hand-bone assessments were made at the entry an at months 6 and 12. Bone X-ray densitometry measurements were made on 16 areas of the hand. Speed of sound was measured across the proximal phalanges of the four fingers. X-rays of both hands were scored according to the modified Sharp's score. At 12 months, patients were classified as rheumatoid arthritis (N = 15; 9 F) or as other rheumatic diseases. RESULTS: We found: 1) significantly decreased bone mineral density (BMD) of the whole hand, in the rheumatoid arthritis group versus the other rheumatic diseases group, at 6 and 12 months (P < 0.05); 2) no significant decrease of bone mineral density (BMD) in other areas in the rheumatoid arthritis group; 3) no significant change of ultrasounds in either group; and 4) no significant correlation between the decrease of BMD in the rheumatoid arthritis group and clinical, biological or radiologic parameters, except for IFNgamma, whose production in whole blood cell culture was lower at entry in the rheumatoid arthritis group. CONCLUSION: DEXA bone assessment in rheumatoid arthritis was able t detect bone loss in the whole hand at 6 months.

Rheumatoid factors, anti-filaggrin antibodies and low in vitro interleukin-2 and interferon-gamma production are useful immunological markers for early diagnosis of community cases of rheumatoid arthritis. A preliminary study.

OBJECTIVE: To determine whether measurements of different autoantibodies (Ab) and cytokines are useful to distinguish very early rheumatoid arthritis (RA) from other inflammatory rheumatisms. METHODS: From a population-based recruitment, 32 patients with very early polyarthritis (median duration: 4 months) were studied. Evaluations at entry (M0), and at 6 (M6) and 12 months (M12). Ab tested: rheumatoid factors (RF) by agglutination methods and ELISA, antiperinuclear factor (APF), antikeratin Ab (AKA), anti-Sa and antinuclear Ab. Cytokine production (TNFalpha, IL2, IFNgamma, IL1beta, IL10) in whole blood cell culture (WBCC) was determined at M0. At M12, patients were classified as having RA (N = 15) or other rheumatic diseases. RESULTS: At M0, AKA/APF and anti-Sa Ab frequencies were low, 13% and 7%, respectively. While most Ab detected at M0 persisted, others appeared during follow-up, particularly APF, which rose from 13 to 40% at M12. At M6, IgM-RF was detected in two RA patients exclusively by ELISA. AKA/APF were found to be highly specific markers for RA (100% specificity). At some time during follow-up, two RF-negative RA patients were AKA-positive. In two patients, AKA and APF were present at M0 before they satisfied ACR criteria. IL2 and IFNgamma production was significantly lower (P < 0.05) for RA patients. CONCLUSION: AKA/APF and anti-Sa Ab were detected in community cases of very early RA. AKA/APF and RF detected by ELISA might contribute to an earlier diagnosis of RA. Low production of IFNgamma and IL2 in WBCC constituted a distinct immunopathological feature in very early RA patients.

Septic Arthritis of the Knee with Toxoplasma gondii in a Patient with Rheumatoid Arthritis.

Toxoplasmosis is a parasitic infection that may affect several viscera. The locomotor system is rarely involved, and no case has been published of a septic arthritis in which Toxoplasma gondii was identified in the cultures of the joint fluid and of the synovial specimen.We describe a patient with septic arthritis of the knee in which Toxoplasma gondii was found by culture in a patient with seropositive rheumatoid arthritis treated with corticosteroids and gold salts who developed multi-visceral toxoplasmosis.

[Postpartum septic arthritis. Two case reports]. / Arthrites septiques du post-partum. A propos de deux cas.

Nongonococcal septic arthritis can occur during the postpartum period. We report two cases, one involving the wrist and the sacroiliac joints and the other the pubic symphysis. The difficulty of initial diagnosis in the postpartum period is emphasized. This pathology is uncommon and may begin insidiously. The sacroiliac joint is particularly at risk for postnatal sepsis, but its deep localization hinders investigations. Besides the classical obstetrical infectious assessment (blood cultures, urine culture, vaginal sample, white blood cell count and CRP) and radiological investigations, joint puncture is needed to isolate the causal infectious agent. Joint immobilization in combination with major 3-month antibiotic therapy is usually successful, generally with no sequellae.

[Treatment of arthroses in the elderly patient]. / Les traitements de l'arthrose du sujet âgé.

BACKGROUND: Elderly subjects with osteoarthritis are treated with analgesic drugs, non-steroidal antiinflammatory drugs (NSAID) and intra-articular corticosteroid injections as well as symptomatic slow acting drugs in osteoarthritis (Sy-SADOA). BASIC REGIMENS: Initial treatment for osteoarthritis pain should be paracetamol, followed by NSAID if necessary, especially in the elderly, because of their adverse effects. EFFICACY: Sy-SADOA are effective on pain and function with a persistent effect, allowing the reduction of analgesic and NSAID dosage.

[Osteoporosis in the elderly. Practical prevention and treatment]. / Ostéoporose du sujet âgé. Prévention et traitement en pratique.

A MAJOR PUBLIC HEALTH ISSUE: Osteoporosis in the elderly limits independence and quality of life. Preventive and curative treatment should be adapted to the patient's age. THERAPEUTIC OBJECTIVES: The goal of preventive like curative treatment is to reduce the risk of fracture. Risk can best be assessed from personal history of fracture or with bone densitometry. THERAPEUTIC METHODS: Non-drug methods are based on physical activity, diet, reduction of alcohol intake or smoking, and limiting the risk of falls. Drugs used include calcium, vitamin D, hormone replacement therapy and bisphosphonates. THERAPEUTIC STRATEGY: Prevention programs should focus first on non-drug methods, adapted to the patient's age. For drug regimens, hormone replacement therapy is rarely used after 70 years of age while calcium and vitamin D are widely used. Drugs inhibiting bone resorption, e.g. bisphosphonates, are added on for curative treatment. After the age of 80 years, the calcium vitamin D combination alone is useful. FOLLOW-UP: A simple surveillance scheme should include a check-up of renal function every year in patients taking bisphosphonates. It is most difficult to assess treatment efficacy on an individual basis.