Objective. In rheumatoid arthritis (RA), telomeres of lymphoid and myeloid cells are ageinappropriately shortened, suggesting excessive turnover of hematopoietic precursor cells (HPCs). The purpose of this study was to examine the functional competence (proliferative capacity, maintenance of telomeric reserve) of CD34؉ HPCs in RA.Methods. Frequencies of peripheral blood CD34؉,CD45؉ HPCs from 63 rheumatoid factorpositive RA patients and 48 controls matched for age, sex, and ethnicity were measured by flow cytometry. Proliferative burst, cell cycle dynamics, and induction of lineage-restricted receptors were tested in purified CD34؉ HPCs after stimulation with early hematopoietins. Telomere sequences were quantified by real-time polymerase chain reaction. HPC functions were correlated with the duration, activity, and severity of RA as well as its treatment.Results. In healthy donors, CD34؉ HPCs accounted for 0.05% of nucleated cells; their numbers were strictly age dependent and declined at a rate of 1.3% per year. In RA patients, CD34؉ HPC frequencies were age-independently reduced to 0.03%. Upon growth factor stimulation, control HPCs passed through 5 replication cycles over 4 days. In contrast, RA-derived HPCs completed only 3 generations. Telomeres of RA CD34؉ HPCs were age-inappropriately shortened by 1,600 bp.

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The treatment armamentarium in rheumatic inflammatory diseases has drastically increased in the last years. Earlier uses of conventional disease-modifying antirheumatic drugs (DMARDs), along with the arrival of newer therapies including the so-called "biologic" agents, have provided better long-term outcomes for patients suffering from these illnesses. Biologic agents have shown efficacy for several diseases and failed in others. Due to a high prevalence of some of these diseases in the elderly population, this age group may also benefit, although treatment will have to be tailored to its special needs. In this mini review, we will discuss the use of these medications in rheumatic diseases with a significant prevalence in the elderly, their proven and potential uses, and the considerations that need to be taken into account when using them in this population.

Treatment strategies in the management of rheumatoid arthritis (RA) have significantly changed in the past decade. The early use of disease-modifying antirheumatic drugs (DMARDs) is the basis of this new treatment strategy. Because these agents alter the natural disease course of RA, early aggressive intervention results in better outcomes with respect to future structural damage and disability. The arrival of the 'biologic agents' era in rheumatology has further improved the therapeutic options in patients with RA. A significant portion of individuals with this ailment are elderly, with approximately one-third of patients experiencing their first symptoms after the age of 60 years. Yet, many elderly patients with RA do not receive optimal treatment. Although the reasons for this have not been completely defined, it seems clinicians are reluctant to use DMARDs in the elderly because of uncertainty regarding their efficacy and safety in this population. The aging process is associated with important changes in drug pharmacokinetics and pharmacodynamics. It appears that the former, mainly through decreased renal clearance, is responsible for an increased incidence of adverse effects with some DMARDs. The old are also more susceptible to infection than the young, making prevention of infectious disease through vaccination of particular importance; however, healthcare professionals should be aware that some DMARDs, including biologic agents, may interfere with responses to vaccination. The available data, although limited, suggest that DMARDs, including some biologic agents, are similarly effective in the old and the young, while maintaining very good adverse effect profiles. Therefore, the elderly with RA should not be excluded from receiving optimal treatment with these medications. At the same time, clinicians must be aware of the possible increased risk of drug toxicities, recognize the need to adjust therapy to match individual patient characteristics (i.e. renal function, co-morbidities, concomitant medication use or polypharmacy), and use the lowest possible effective dosage. This review describes the special considerations to be taken into account when administering conventional (synthetic) or biologic DMARDs to elderly patients with RA.

We present a case of arthritis apparently induced by the administration of intravenous bisphosphonates in a 51-year-old white woman with metastatic breast carcinoma. She presented with bilateral knee pain and effusions on 2 separate occasions after receiving aminobisphosphonates. Synovial fluid analysis was negative for infection, metastasis, or crystals. Her symptoms resolved after the medication was discontinued and recurred after the patient was rechallenged with a medication from the same drug class. The administration of aminobisphosphonates has been associated with an acute-phase response in several in vivo studies. The mechanism of action is thought to be that aminobisphosphonates transiently stimulate the production of proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha. Rheumatologists should be aware of this possible cause of arthropathy.

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