Safety profile of drugs used in the treatment of osteoporosis: a systematical review of the literature.

The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction

Improvement of pain and regional osteoporotic changes in the foot and ankle by low-dose bisphosphonate therapy for complex regional pain syndrome type I: a case series

<p>Abstract</p> <p>Introduction</p> <p>Complex regional pain syndrome is characterized by pain, allodynia, hyperalgesia, edema, signs of vasomotor instability, movement disorders, joint stiffness, and regional osteopenia. It is recognized to be difficult to treat, despite various methods of treatment, including physiotherapy, calcitonin, corticosteroids, sympathetic blockade, and nonsteroidal anti-inflammatory drugs. Pathophysiologically, complex regional pain syndrome reveals enhanced regional bone resorption and high bone turnover, and so bisphosphonates, which have a potent inhibitory effect on bone resorption, were proposed for the treatment of complex regional pain syndrome.</p> <p>Case presentation</p> <p>A 48-year-old Japanese man with complex regional pain syndrome type I had severe right ankle pain with a visual analog scale score of 59 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for five months. Radiographs showed marked regional osteoporotic changes and bone scintigraphy revealed a marked increase in radioactivity in his ankle. One month after the start of oral administration of risedronate (2.5 mg per day), his bone pain had fallen from a VAS score of 59 out of 100 to 18 out of 100. Bone scintigraphy at 12 months showed a marked reduction in radioactivity to a level comparable to that in his normal, left ankle. On the basis of these results, the treatment was discontinued at 15 months. At 32 months, our patient had almost no pain and radiographic findings revealed that the regional osteoporotic change had returned to normal.</p> <p>A second 48-year-old Japanese man with complex regional pain syndrome type I had severe right foot pain with a visual analog scale score of 83 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for nine months. Radiographs showed regional osteoporotic change in his phalanges, metatarsals, and tarsals, and bone scintigraphy revealed a marked increase in radioactivity in his foot. One month after the start of oral administration of alendronate (35 mg per week), his bone pain had fallen from a visual analog scale score of 83 out of 100 to 30 out of 100 and, at nine months, was further reduced to 3 out of 100. The treatment was discontinued at 15 months because of successful pain reduction. At 30 months, our patient had no pain and the radiographic findings revealed marked improvement in regional osteoporotic changes.</p> <p>Conclusions</p> <p>We believe low-dose oral administration of bisphosphonate is worth considering for the treatment of idiopathic complex regional pain syndrome type I accompanied by regional osteoporotic change.</p

The relationship between educational level and bone mineral density in postmenopausal women

BACKGROUND: This study describes the influence of educational level on bone mineral density (BMD) and investigating the relationship between educational level and bone mineral density in postmenopausal women. METHODS: A total of 569 postmenopausal women, from 45 to 86 years of age (mean age of 60.43 ± 7.19 years) were included in this study. A standardized interview was used at the follow-up visit to obtain information on demographic, life-style, reproductive and menstrual histories such as age at menarche, age at menopause, number of pregnancies, number of abortions, duration of menopause, duration of fertility, and duration of lactation. Patients were separated into four groups according to the level of education, namely no education (Group 1 with 209 patients), elementary (Group 2 with 222 patients), high school (Group 3 with 79 patients), and university (Group 4 with 59 patients). RESULTS: The mean ages of groups were 59.75 ± 7.29, 61.42 ± 7.50, 60.23 ± 7.49, and 58.72 ± 7.46, respectively. Spine BMD was significant lower in Group 1 than that of other groups (p < 0.05). Trochanter and ward's triangle BMD were the highest in Group 4 and there was a significant difference between Group 1 and 4 (p < 0.05). The prevalence of osteoporosis showed an inverse relationship with level of education, ranging from 18.6% for the most educated to 34.4% for the no educated women (p < 0.05). Additionally, there was a significant correlation between educational level and spine BMD (r = 0.20, p < 0.01), trochanter BMD (r = 0.13, p < 0.01), and ward's BMD (r = 0.14, p < 0.01). CONCLUSIONS: The results of the study suggest that there is a significant correlation between educational level and BMD. Losses in BMD for women of lower educational level tend to be relatively high, and losses in spine and femur BMD showed a decrease with increasing educational level

Pain prediction by serum biomarkers of bone turnover in people with knee osteoarthritis: an observational study of TRAcP5b and cathepsin K in OA

Objectives: To investigate serum biomarkers, tartrate resistant acid phosphatase 5b (TRAcP5b) and cathepsin K, indicative of osteoclastic bone resorption, and their relationship to pain and pain change in knee osteoarthritis (OA). Methods: Sera and clinical data were collected from 129 people (97 with 3-year follow-up) with knee OA from the Prediction of Osteoarthritis Progression (POP) cohort. Knee OA-related outcomes in POP included: WOMAC pain, NHANES I (pain, aching and stiffness), subchondral sclerosis, and radiographically determined tibiofemoral and patellofemoral OA. Two putative osteoclast biomarkers were measured in sera: TRAcP5b and cathepsin K. Medial tibia plateaux were donated at knee arthroplasty for symptomatic OA (n=84) or from 16 post mortem controls from the Arthritis Research UK (ARUK) Pain Centre joint tissue repository. Osteoclasts were stained for TRAcP within the subchondral bone of the medial tibia plateaux. Results: Serum TRAcP5b activity, but not cathepsin K-immunoreactivity, was associated with density of TRAcP-positive osteoclasts in the subchondral bone of medial tibia plateaux. TRAcP-positive osteoclasts were more abundant in people with symptomatic OA compared to controls. Serum TRAcP5b activity was associated with baseline pain and pain change. Conclusions: Our observations support a role for subchondral osteoclast activity in the generation of OA pain. Serum TRAcP5b might be a clinically relevant biomarker of disease activity in OA

The Oslo Health Study: Is bone mineral density higher in affluent areas?

<p>Abstract</p> <p>Background</p> <p>Based on previously reported differences in fracture incidence in the socioeconomic less affluent Oslo East compared to the more privileged West, our aim was to study bone mineral density (BMD) in the same socioeconomic areas in Oslo. We also wanted to study whether possible associations were explained by socio-demographic factors, level of education or lifestyle factors.</p> <p>Methods</p> <p>Distal forearm BMD was measured in random samples of the participants in The Oslo Health Study by single energy x-ray absorptiometry (SXA). 578 men and 702 women born in Norway in the age-groups 40/45, 60 and 75 years were included in the analyses. Socioeconomic regions, based on a social index dividing Oslo in two regions – East and West, were used.</p> <p>Results</p> <p>Age-adjusted mean BMD in women living in the less affluent Eastern region was 0.405 g/cm²and significantly lower than in West where BMD was 0.419 g/cm². Similarly, the odds ratio of low BMD (Z-score ≤ -1) was 1.87 (95% CI: 1.22–2.87) in women in Oslo East compared to West. The same tendency, although not statistically significant, was also present in men. Multivariate analysis adjusted for education, marital status, body mass index, physical inactivity, use of alcohol and smoking, and in women also use of post-menopausal hormone therapy and early onset of menopause, did hardly change the association. Additional adjustments for employment status, disability pension and physical activity at work for those below the age of retirement, gave similar results.</p> <p>Conclusion</p> <p>We found differences in BMD in women between different socioeconomic regions in Oslo that correspond to previously found differences in fracture rates. The association in men was not statistically significant. The differences were not explained by socio-demographic factors, level of education or lifestyle factors.</p

Regional differences of vitamin D deficiency in rheumatoid arthritis patients in Italy

Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA). Aim of this study was to evaluate the prevalence of vitamin D deficiency among the different Italian regions and whether these variations are associated with different severity of the disease. The study includes 581 consecutive RA patients (464 women), not taking vitamin D supplements, from 22 Italian rheumatology centres uniformly distributed across Italy. Together with parameters of disease activity (disease activity score 28), functional impairment (activities of daily living and health assessment questionnaire disability index) and mean sun exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a centralized laboratory. Vitamin D deficiency (25OHD level <20 ng/mL) was very frequent among RA patients; its prevalence was 60%, 52% and 38% in southern, central and northern Italy, respectively. Mean disease activity and disability scores were worse in southern regions of Italy. These scores were inversely related to 25OHD levels and this correlation remained statistically significant after adjusting for both body mass index (BMI) and sun exposure time. However, disease severity remained significantly higher in southern regions versus central-northern Italy after adjustment also for serum 25OHD levels, age and BMI. In RA Italian patients there are significant regional differences in the prevalence of vitamin D deficiency explained by different BMI, and sun exposure time, and inversely associated with disease activity and disability scores

Whey protein reduces early life weight gain in mice fed a high-fat diet.

An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P<0.001-0.05). Hereafter weight gain was similar resulting in a 15% lower final body weight in the whey group relative to casein (34.0±1.0 g vs. 40.2±1.3 g, P<0.001). Food intake was unaffected by protein source throughout the study period. Fasting insulin was lower in the whey group (P<0.01) and glucose clearance was improved after an oral glucose challenge (P<0.05). Plasma cholesterol was lowered by whey compared to casein (P<0.001). The composition of the fecal microbiota differed between high- and low-fat groups at 13 weeks (P<0.05) whereas no difference was seen between whey and casein. In conclusion, whey initially reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota composition. Further studies are needed to clarify the mechanisms behind the metabolic effects of whey

Guidelines for the diagnosis, prevention and treatment of osteoporosis

The guidelines for the osteoporosis management were first drafted by a working group and then critically evaluated by the board of SIOMMMS. The most relevant points are: Definition: Osteoporosis is defined as a quantitative and qualitative deterioration of bone tissue leading to increased risk of fracture. Postmenopausal and senile osteoporosis are defined as primitive. Diagnosis: The cornerstone for the diagnosis of osteoporosis is the measurement of bone mineral density (BMD) by DXA (dual-energy X-ray absortiometry) at the femoral neck with T-score values -2.5 is usually not justified. Pharmacological intervention: The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk. This is the case only when the risk of fracture is rather high. FRAX™ is recognized as a useful tool for easily estimate the long-term fracture risk. SIOMMMS with these guidelines is committed to validate and further develop this diagnostic tool