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Compliance to oral bisphosphonates is suboptimal, with negative consequences of increased healthcare utilization and less effective fracture risk reduction. Extending dose interval increased adherence only moderately. We used literature derived from multiple chronic conditions to examine the problem of noncompliance with osteoporosis medication. We reviewed the literature on adherence to osteoporosis medication as well as that across multiple chronic conditions to understand what is known about the cause of the poor adherence. Poor compliance to oral medications is due mostly, not to forgetfulness, but to deliberate choice. Gender differences and style of healthcare management also play a role. Preliminary data suggest psychobehavioral interventions may help to improve motivation. We need to understand better reasons for poor compliance before effective interventions can be developed. Forgetfulness is only a small part of poor compliance. Patient preferences must be considered in medication decision making.

Bazedoxifene (Conbriza®, Viviant®) is the first third-generation selective estrogen receptor modulator (SERM) and it is approved for the treatment of postmenopausal osteoporosis in the EU and Japan. Bazedoxifene contains an indole-based core binding domain that binds with high affinity to estrogen receptors and exhibits favourable effects on bone and lipid profiles, with no clinically relevant endometrial or breast stimulation. Oral bazedoxifene once daily reduced the incidence of new vertebral fractures in patients with postmenopausal osteoporosis in a large, well designed trial of 3 years' duration; both bazedoxifene and raloxifene were significantly more effective than placebo. Neither bazedoxifene nor raloxifene reduced the incidence of nonvertebral fractures in the overall study population; however, bazedoxifene, but not raloxifene, reduced the rate of nonvertebral fractures in high- risk patients. Moreover, data from patients who continued to receive the drug during a 2-year extension phase of this trial indicate that bazedoxifene continues to provide protection against new vertebral fractures for up to 5 years. Bazedoxifene also increases bone mineral density and reduces the levels of bone turnover markers. Bazedoxifene was generally well tolerated and did not detrimentally affect the reproductive tract or breast tissue in clinical trials, thereby demonstrating a favourable risk-benefit profile. A pharmacoeconomic analysis conducted from an EU perspective predicted bazedoxifene to be cost effective in some EU countries. Therefore, bazedoxifene presents another useful option for the treatment of postmenopausal osteoporosis, especially in those at high risk for osteoporotic fracture. [ABSTRACT FROM AUTHOR]

To determine the role of inflammation in amyloidogenesis, we have studied the degradation of human serum amyloid A (SAA) protein by purified preparations of human blood polymorphonuclear leucocytes (PMN) and monocytes. When both PMN and monocytes were incubated in SAA-containing medium, the concentration of SAA as measured by a competitive anti-AA radioimmunoassay decreased over time. The rate of decrease of SAA was similar for both monocytes and PMN and there were no differences between four patients with amyloidosis and three normal controls. Resting PMN from normal volunteers were able to degrade SAA to smaller acid-soluble peptides within 16 hr while zymosan-activated PMN produced significant degradation within 1 hr (31%-50%). The supernatants from zymosantreated PMN also caused marked SAA degradation within 1 hr. The following enzyme inhibitors were able to prevent degradation of SAA by PMN supernatants; phenylmethylsulphonyl fluoride, a serine esterase inhibitor; α1, anti-trypsin and soybean trypsin inhibitor; and acetyl-ala-ala-pro-val-chloromethyl ketone, an elastase inhibitor. The ability of a neutral lysosomal enzyme to degrade SAA was further confirmed by showing that purified PMN elastase significantly degraded 125I-SAA. We conclude that PMN contain one or more lysosomal enzymes capable of degrading SAA, an apoprotein of HDL3 serum lipoproteins. Alteration in SAA proteolysis by activated PMN may contribute to the deposition of amyloid fibrils in the tissues of patients with chronic inflammatory disease. [ABSTRACT FROM AUTHOR]

During a recent 5-month period, 16 intravenous heroin users were hospitalized with a previously unrecognized complication of drug abuse. The characteristic symptoms were similar in all patients and included fever, paraspinal myalgias, and periarthritis. There was no evidence of bacterial infection, hepatitis, or drug abstinence as the cause of these musculoskeletal symptoms. Continued heroin use was associated with progressive musculoskeletal symptoms, while discontinuation of heroin use resulted in complete recovery. Antibiotics did not affect the outcome, and the syndrome was self-limited in all hospitalized patients. The pathogenesis of this syndrome is unknown but may be related to the heroin, which was described as brown by the patients, or an adulterant. [ABSTRACT FROM AUTHOR]

Compliance to oral bisphosphonates is suboptimal, with negative consequences of increased healthcare utilization and less effective fracture risk reduction. Extending dose interval increased adherence only moderately. We used literature derived from multiple chronic conditions to examine the problem of noncompliance with osteoporosis medication. We reviewed the literature on adherence to osteoporosis medication as well as that across multiple chronic conditions to understand what is known about the cause of the poor adherence. Poor compliance to oral medications is due mostly, not to forgetfulness, but to deliberate choice. Gender differences and style of healthcare management also play a role. Preliminary data suggest psychobehavioral interventions may help to improve motivation. We need to understand better reasons for poor compliance before effective interventions can be developed. Forgetfulness is only a small part of poor compliance. Patient preferences must be considered in medication decision making.

The eValuation of IBandronate Efficacy (VIBE) head-to-head database fracture study compared fracture rates between patients treated with monthly ibandronate and weekly oral bisphosphonates (BPs). This large study included women >/=45 years old, newly prescribed monthly oral ibandronate or weekly oral alendronate or risedronate, and without malignancy or Paget's disease of bone. The primary analysis included patients who were adherent to treatment during the first 90 days after the index date. The risks of hip, nonvertebral, vertebral and any clinical fracture were compared using Cox proportional hazards models and adjusted for potential confounding factors. A secondary, "intent-to-treat" analysis included all patients who received at least one BP prescription. Sensitivity analyses based on the primary analysis compared patients receiving ibandronate with patients receiving weekly alendronate or risedronate separately, and explored the effect of excluding patients with potential confounding factors from the analysis. Further sensitivity analyses varied the requirement for adherence during the first 90 days after the index date. The primary analysis population included 7345 monthly ibandronate and 56,837 weekly BP patients. Fracture rates after the 12-month observational period were <2% and fracture risk was not significantly different between patients receiving monthly ibandronate or weekly BPs for hip, nonvertebral or any clinical fracture (adjusted relative risk: hip=1.06, p=0.84; nonvertebral=0.88, p=0.255; any clinical fracture=0.82, p=0.052). Ibandronate patients had a significantly lower risk of vertebral fracture than weekly BP patients (adjusted relative risk 0.36, 95% confidence interval 0.18-0.75, p=0.006). In the secondary, "intent-to-treat" analysis, relative risks of fracture were not significantly different between treatment groups for any fracture type. The results of the sensitivity analyses were generally consistent with the primary analysis. This retrospective cohort study found that patients treated with oral monthly ibandronate or weekly BPs (alendronate and risedronate) had similar, low risks of hip fracture, nonvertebral fracture and any clinical fracture. Ibandronate patients had a significantly lower relative risk of vertebral fracture than weekly BP patients; the clinical implications of these findings require further exploration and validation.

Objective: To examine the effect of both prevalent and incident vertebral fractures on health-related quality of life (HRQOL) in postmenopausal women with osteoporosis and to characterize the effect of prevalent vertebral fractures on HRQOL with respect to number, location, severity, and adjacency., Methods: Participants were a subset of women (n = 1,395, mean age 68.5 years) from the Multiple Outcomes of Raloxifene Evaluation trial who had low bone mineral density and/or prevalent vertebral fractures. Vertebral fractures were measured by radiography at baseline, 2 years, and 3 years. HRQOL was assessed using the Osteoporosis Assessment Questionnaire (OPAQ), a validated disease-targeted instrument, at baseline and annually for 3 years., Results: Both prevalent and incident radiographic vertebral fractures were associated with decreased HRQOL. At baseline, women with a prevalent vertebral fracture had significantly lower OPAQ scores on physical function, emotional status, clinical symptoms, and overall HRQOL compared with women without a prevalent fracture (all P < 0.01). HRQOL scores were lower with each subsequent fracture. The effect of prevalent vertebral fracture was dependent on the location within the spine and was strongest in the lumbar region (L1-L4). Incident vertebral fractures significantly decreased OPAQ scores on physical function, emotional status, clinical symptoms, and overall HRQOL (all P < 0.001)., Conclusion: Our findings demonstrate the importance of treating postmenopausal women who have prevalent vertebral fractures to prevent further decreases in HRQOL associated with subsequent incident vertebral fracture.