Are disease duration and degree of functional impairment determinants of bone loss in rheumatoid arthritis?

One hundred and five patients with rheumatoid arthritis treated with a variety of antirheumatic drugs, excepting glucocorticoids, were stratified according to the degree of functional impairment (functional classes I to IV) and duration of the disease (0-3 years; 4-8 years; and greater than 8 years). The variables investigated were distal forearm bone mineral content (BMC), biochemical markers of bone formation: serum alkaline phosphatase and serum bone gamma-carboxyglutamic acid containing protein (BGP) and biochemical markers of bone resorption: fasting urinary calcium and fasting urinary hydroxyproline. Significant relationships were found between BMC and functional impairment and duration of the disease. Indices of bone formation and bone resorption rose with increasing functional impairment, particularly those of bone resorption. It is concluded that disability induces osteopenia in rheumatoid arthritis by increasing the bone turnover with a more marked increased in resorption than in the formation processes. The effect of the disease duration is merely that of adding more years of functional impairment.     

QCT measures of bone strength at the thoracic and lumbar spine: the Framingham Study

We used volumetric quantitative computed tomography (QCT) scans to evaluate volumetric bone density (vBMD), geometry, and strength in the thoracic (T8 to T10) and lumbar (L3 to L5) spine and determined how these parameters varied with age, sex, and spinal region. Participants included 690 participants of the Framingham Study, 40 to 87 years old (mean, 61 years). In both women and men, trabecular vBMD declined with age similarly for lumbar and thoracic regions, whereas cortical vBMD and integral vBMD, vertebral strength, and compressive force declined more at the lumbar spine than thoracic spine (interaction, p < 0.01). Notably, in men, cortical vBMD increased (β = 0.0004, p = 0.01), and vertebral strength did not change (β = 1.9305, p = 0.66) at the thoracic spine with age. In both women and men, vertebral cross-sectional area increased less and the factor-of-risk increased more with age at the lumbar than at the thoracic region (interaction, p < 0.01). For example, in women, the factor-of-risk for forward flexion increased (worsened) with age 6.8-fold more in the lumbar spine (β = 0.0157), compared with the thoracic spine (β = 0.0023). vBMD and vertebral strength declined more and the factor-of-risk increased more with age in women than men (interaction, p < 0.01). For instance, integral vBMD for the lumbar spine declined 36% from 40 to 75 years of age in women compared with 18% in men. There was little or no age-related change in the forces applied to the thoracic vertebrae in either women or men. Age-related changes were greater in the lumbar spine than in the thoracic region and greater in women than men. Whereas women lost bone density and strength at both the thoracic and lumbar spine, in men, vertebral strength declined only at the lumbar spine. Our study confirms the importance of evaluating determinants of vertebral strength in both the thoracic and lumbar spine and in both women and men to understand mechanisms underlying the structural failure of vertebral bodies with aging.     

Individualizing osteoporosis therapy

Guidelines for osteoporosis treatment are available; however, these guidelines suggest when to treat patients, without specific recommendations on what drugs to prescribe in various situations. Choice of osteoporosis therapy should be individualized based on consideration of the efficacy, safety, cost, convenience (i.e., dosing regimen and delivery), and other non-osteoporosis-related benefits associated with each agent. Bisphosphonates, administered orally or intravenously, should be considered first-line therapy, particularly in older patients, owing to their efficacy across multiple skeletal sites; however, there are potential short- and long-term safety concerns. Selective estrogen receptor modulators should be considered for younger postmenopausal women at greater risk for vertebral than hip fractures or as second-line therapy in women who cannot tolerate first-line therapies. Low-dose hormone therapy may be appropriate as prevention in women with menopausal symptoms at lower fracture risk. Calcitonin, with its relatively benign safety profile, may be appropriate for elderly women who may have difficulty following the complex dosing schedules of oral bisphosphonates. Anabolic therapies such as teriparatide should be considered for high-risk patients. Strontium ranelate (approved outside of North America), with both anabolic and antiresorptive properties, may be appropriate for women who cannot tolerate or are unable to take bisphosphonates. Denosumab is a monoclonal antibody appropriate for women at high fracture risk or who have failed other osteoporosis therapies, and may be considered in patients with renal insufficiency. It will be important to incorporate newer agents (e.g., bazedoxifene, tissue selective estrogen complex) into this individualized treatment paradigm to optimize clinical outcomes in patients with osteoporosis.     

Unusual benign paratesticular tumor in an infant mimicking rhabdomyosarcoma

Paratesticular tumors are extremely rare, with paratesticular rhabdomyosarcoma being the most common finding. A 6-month-old boy presented with an asymptomatic, right intrascrotal mass whereby the testicle was surrounded by a friable lipomatous tumor. Frozen section revealed an inflammatory process, negative for malignancy. Tumorectomy with vaginal resection was performed, maintaining the testicle and excretory ducts. Histopathologic findings showed a juvenile xanthogranuloma, a non-Langerhans histiocytosis commonly described in infants in the skin and skeletal muscle. The patient is doing well 2 years after surgery and is the first such case reported in the literature with successful conservative treatment.     

Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?

Introduction and hypothesis Epidemiological observations suggest links between osteoporosis and risk of acute cardiovascular events and vice versa. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. We investigated whether serum lipids and polymorphism in the ApoE gene modifying serum lipids could be a biological linkage. Methods This was an observational study including 1176 elderly women 60–85 years old. Women were genotyped for epsilon (ɛ) allelic variants of the ApoE gene, and data concerning serum lipids (total cholesterol, triglycerides, HDL-C, LDL-C, apoA1, ApoB, Lp(a)), hip and spine BMD, aorta calcification (AC), radiographic vertebral fracture and self-reported wrist and hip fractures, cardiovascular events together with a wide array of demographic and lifestyle characteristics were collected. Results Presence of the ApoE ɛ4 allele had a significant impact on serum lipid profile, yet no association with spine/hip BMD or AC could be established. In multiple regression models, apoA1 was a significant independent contributor to the variation in AC. However, none of the lipid components were independent contributors to the variation in spine or hip BMD. When comparing the women with or without vertebral fractures, serum triglycerides showed significant differences. This finding was however not applicable to hip or wrist fractures. After adjustment for age, severe AC score (≥6) and/or manifest cardiovascular disease increased the risk of hip but not vertebral or wrist fractures. Conclusion The contribution of serum lipids to the modulators of BMD does not seem to be direct but rather indirect via promotion of atherosclerosis, which in turn can affect bone metabolism locally, especially when skeletal sites supplied by end-arteries are concerned. Further studies are needed to explore the genetic or environmental risk factors underlying the association of low triglyceride levels to vertebral fractures.     

Should subchondral bone turnover be targeted when treating osteoarthritis?

OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This review summarizes emerging observations from cell biology to preliminary clinical trials, describing interactions between the bone and cartilage components. We speculate whether a treatment for OA would be possible without targeting the bone compartment? METHODS: Peer-reviewed articles found using pre-defined search criteria and published in the PubMed database until June 2007 are summarized. In addition, abstracts from the OsteoArthritis Research Society International (OARSI) conferences in the time period 2000-2007 were included. RESULTS: Bone and cartilage health seem to be tightly associated. Ample evidence is found for bone changes during progression of OA, including, but not limited to, increased turnover in the subchondral bone, thinning of the trabecular structure, osteophytes, bone marrow lesions and sclerosis of the subchondral plate. In addition, a range of investigations has described secondary positive effects on cartilage health when bone resorption was suppressed, or deterioration of the cartilage when resorption is increased. CONCLUSION: An optimal treatment for OA might include targeting both the bone and cartilage compartments. Hence, as several cell systems are to be targeted in a safe manner, limited options seem possible.     

Sacral nerve stimulation for treatment of fecal incontinence in a patient with muscular dystrophy: report of a case

Fecal incontinence is a common condition that causes major impairment of social life. Sacral nerve stimulation is a promising treatment in idiopathic fecal incontinence when conventional treatments have failed. However, new indications for sacral nerve stimulation are emerging. The present case shows that sacral nerve stimulation for treatment of fecal incontinence may be justified in other diseases in which fecal incontinence is a major problem.