Purpose: To evaluate serum 25-hydroxyvitamin D 25(OH)D concentrations and factors related to vitamin D inadequacy in postmenopausal North American women receiving therapy to treat or prevent ...osteoporosis.
Methods: Serum 25(OH)D and PTH were obtained in 1536 community-dwelling women between November 2003 and March 2004. Multivariate logistic regression was used to assess risk factors for suboptimal (<30 ng/ml) 25(OH)D.
Results: Ninety-two percent of study subjects were Caucasian, with a mean age of 71 yr. Thirty-five percent resided at or above latitude 42° north, and 24% resided less than 35° north. Mean (sd) serum 25(OH)D was 30.4 (13.2) ng/ml: serum 25(OH)D was less than 20 ng/ml in 18%; less than 25 ng/ml in 36%; and less than 30 ng/ml in 52%. Prevalence of suboptimal 25(OH)D was significantly higher in subjects who took less than 400 vs. 400 IU/d or more vitamin D. There was a significant negative correlation between serum PTH concentrations and 25(OH)D. Risk factors related to vitamin D inadequacy included age, race, body mass index, medications known to affect vitamin D metabolism, vitamin D supplementation, exercise, education, and physician counseling regarding vitamin D.
Conclusions: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.
Boosted protease inhibitor regimens combine ritonavir with a second, ‘boosted’ protease inhibitor to enhance patient exposure to the latter agent, thereby preventing or overcoming resistance and ...allowing less frequent dosing, potentially improving adherence. The advantages offered by ritonavir boosting are primarily attributable to the drug’s pharmacokinetic properties. Ritonavir’s inhibition of the cytochrome P-450 CYP3A4 enzyme reduces the metabolism of concomitantly administered protease inhibitors and changes their pharmacokinetic parameters, including area under the curve (AUC), maximum concentration (Cmax), minimum concentration (Cmin) and half-life (t1/2). As a result, the bioavailability of the boosted protease inhibitor is increased and improved penetration into HIV reservoirs may be achieved. Boosted protease inhibitor regimens that utilize a low dose of ritonavir (100–200 mg) appear to offer the best balance of efficacy and tolerability. At this dose, ritonavir boosts the bioavailability of the second protease inhibitor without contributing significantly to the side effect profile of the regimen. In clinical trials, regimens boosted with low dose ritonavir have demonstrated high levels of viral suppression in both antiretroviral naïve patients and patients who previously failed antiretroviral therapy, including protease inhibitor therapy. Side effects observed have generally been similar to those associated with the boosted protease inhibitor. Based upon their enhanced drug exposure and demonstrated efficacy, the boosted ritonavir regimens should be among the first options considered for use in clinical practice.
Background:
Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation.
Objectives:
This study aimed to determine ...patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the patients believed was more convenient and would be easier to comply with for a long period.
Methods:
This was a multicenter, randomized, open-label, preference study in which postmenopausal women with osteoporosis were enrolled to receive 9 weeks of treatment in crossover fashion (4 weeks with each study regimen separated by a 1-week washout period). The study regimens included once-weekly alendronate 70 mg and once-daily alendronate 10 mg. The primary and secondary end points were assessed with a questionnaire completed by the patient. Adverse events (AEs) were recorded to assess patient tolerability of the study medications.
Results:
A total of 324 patients met the eligibility requirements; 288 were randomized to treatment, 287 (mean age, 64.8 years) received treatment, 272 completed the questionnaire, and 266 completed the study. Of the patients who completed the questionnaire, 235 patients preferred the 70-mg once-weekly dosing regimen compared with the 10-mg once-daily regimen (86.4% vs 9.2%;
P < 0.001). Most patients also believed that once-weekly dosing was more convenient than once-daily dosing (89.0% vs 7.7%;
P < 0.001) and would allow them to achieve better long-term compliance (87.5% vs 8.5%;
P < 0.001). Clinical AEs were reported in 30.7% of patients treated with once-weekly alendronate and 30% of patients treated with once-daily alendronate, with no significant differences between treatments.
Conclusion:
When once-weekly alendronate 70 mg was compared with once-daily alendronate 10 mg in this study, 70-mg once-weekly alendronate was the preferred dosing regimen.
To compare efficacy among 1578 patients with osteoarthritis randomized to take acetaminophen 4000 mg (n=269), celecoxib 200 mg (n=523), rofecoxib 12.5 mg (n=259), or rofecoxib 25 mg (n=527) in a ...double blind trial Vioxx, Acetaminophen, Celecoxib Trial (VACT2). Results were also pooled with the similarly designed VACT1 trial.
Patients evaluated over Days 1 to 6 and 6 weeks with Patient Global Assessment of Response to Therapy (PGART) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index.
For VACT2, median time to good or excellent PGART response was 6, 5, 4, and 3 days for acetaminophen, celecoxib, rofecoxib 12.5 mg, and rofecoxib 25 mg (COX-2 inhibitors vs acetaminophen, p<or=0.035; rofecoxib 25 mg vs celecoxib, p=0.01). WOMAC response over the first 6 days was greater (p < 0.05) with both rofecoxib doses than acetaminophen and celecoxib. At Week 6, all COX-2 inhibitors provided significantly greater efficacy than acetaminophen. Good or excellent PGART was numerically, but not significantly, greater with rofecoxib 25 mg (55.4%) than celecoxib (50.6%) at Week 6; a significant difference was seen at Weeks 2 (6.9, p=0.022) and 4 (6.7, p=0.027) and over 6 weeks with analysis of all 5 PGART categories of response (p=0.035). Rofecoxib 25 mg provided greater response (p<0.05) than celecoxib on WOMAC subscales. Pooled analysis of VACT1/VACT2 demonstrated greater PGART (p=0.023) with rofecoxib 25 mg (56.1%) than celecoxib (49.8%) at 6 weeks and greater response to all other PGART and WOMAC endpoints, and confirmed superiority of COX-2 inhibitors to acetaminophen. Overall, tolerability of the study medications was generally good and similar. There was no significant difference between treatment groups in the percentage of patients who experienced a clinical adverse experience (AE). The incidence of discontinuations due to an AE was significantly lower with celecoxib (2.5%) compared to rofecoxib 25 mg (6.3%, p=0.004) or acetaminophen (7.8%, p< 0.001), and did not differ significantly from rofecoxib 12.5 mg (4.6%). Discontinuation rates due to edema and hypertension related AE were similar among all COX-2 inhibitors.
Rofecoxib and celecoxib provided superior efficacy to acetaminophen. There was a more rapid and greater response with rofecoxib 25 mg than celecoxib 200 mg. Rofecoxib 12.5 mg demonstrated greater efficacy than celecoxib 200 mg over the first 6 days, and was similar over 6 weeks. All study medications were generally well tolerated.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a dose-related risk of cardiovascular, renal, and gastrointestinal adverse events (AEs). Topical NSAIDs produce lower systemic NSAID ...exposure compared with oral NSAIDs, offering potential benefits.
To evaluate the safety of topical diclofenac sodium 1% gel (DSG) for knee and hand osteoarthritis (OA) in older and younger patients and in patients with versus without comorbid hypertension, type 2 diabetes, or cerebrovascular or cardiovascular disease.
Post hoc analysis of pooled data from 5 randomized, double-blind, placebo-controlled trials involving 1426 patients (aged ≥35 years) with mild to moderate OA of the knee and 783 patients (aged ≥40 years) with mild to moderate OA of the hand. Patients applied 4 g of DSG or vehicle to affected knees QID for 12 weeks or 2 g of DSG or vehicle to affected hands QID for 8 weeks.
In patients with knee OA, the percentage with ≥1 adverse event was similar in patients aged <65 years (56.6%) versus ≥65 years (55.8%) and was similar in patients with versus without comorbid hypertension (53.4% vs 59.0%, respectively), type 2 diabetes mellitus (50.0% vs 57.2%), or cerebrovascular or cardiovascular disease (53.8% vs 56.5%). In patients with hand OA, the percentage with ≥1 AE was similar in patients aged ≥65 years (42.7%) versus <65 years (39.1%) and was similar in patients with versus without hypertension (39.6% vs 41.7%, respectively), lower in patients with versus without type 2 diabetes mellitus (28.0% vs 41.6%), and higher in patients with versus without cerebrovascular or cardiovascular disease (48.5% vs 39.2%). Gastrointestinal, cardiovascular, and renal AEs were rare and did not differ according to age or comorbidity. Application site reactions were the primary cause for the greater frequency of AEs with DSG versus vehicle.
The similar and low rates of AEs in DSG-treated patients aged ≥65 years and <65 years and in those with and without comorbid hypertension, type 2 diabetes, or cerebrovascular or cardiovascular disease suggest that DSG treatment is generally well tolerated.
To compare the efficacy and tolerability of once-weekly (OW) alendronate (ALN) 70 mg and raloxifene (RLX) 60 mg daily in the treatment of postmenopausal osteoporosis.
This 12-month, randomized, ...double-blind study enrolled 456 postmenopausal women with osteoporosis (223 ALN, 233 RLX) at 52 sites in the United States. Efficacy measurements included lumbar spine (LS), total hip, and trochanter bone mineral density (BMD) at 6 and 12 months, biochemical markers of bone turnover, and percent of women who maintained or gained BMD in response to treatment. The primary endpoint was percent change from baseline in LS BMD at 12 months. Adverse experiences were recorded to assess treatment safety and tolerability.
Over 12 months, OW ALN produced a significantly greater increase in LS BMD (4.4%, P < 0.001) than RLX (1.9%). The percentage of women with > or = 0% increase in LS BMD (ALN, 94%; RLX, 75%; P < 0.001) and > or =3% increase in LS BMD (ALN, 66%; RLX, 38%; P < 0.001) were significantly greater with ALN than RLX. Total hip and trochanter BMD increases were also significantly greater (P < or =0.001) with ALN. Greater (P < 0.001) reductions in N-telopeptide of type I collagen and bone-specific alkaline phosphatase were achieved with ALN compared with RLX at 6 and 12 months. No significant differences in the incidence of upper gastrointestinal or vasomotor adverse experiences were seen.
ALN 70 mg OW produced significantly greater increases in spine and hip BMD and greater reductions in markers of bone turnover than RLX over 12 months. A greater percentage of women maintained or gained BMD on ALN than RLX. Both medications had similar safety and tolerability profiles.
SUMMARY
Objective: To compare the effects of alendronate (ALN) 70mg once weekly (OW) and risedronate (RIS) 5mg daily between-meal dosing on biochemical markers of bone turnover and bone mineral ...density (BMD) in postmenopausal women with osteoporosis.
Research design and methods: This was a 3-month, randomised, double-blind, placebo-controlled study with a double-blind extension to 12 months. The study enrolled 549 postmenopausal women (ALN 219, RIS 222 and placebo (PBO) 108) who were >60 years of age at outpatient centres.
Main outcome measures: The primary endpoint was reduction in urine N-telopeptides of type 1 collagen (NTx) corrected for creatinine level at 3 months. Secondary parameters included change in BMD at the spine and hip at 6 and 12 months, NTx at 1,6 and 12 months, and serum bone-specific alkaline phosphatase (BSAP) at 1, 3, 6 and 12 months. Adverse experiences (AEs) were recorded throughout the study for an assessment of treatment safety profiles and tolerability.
Results: Over 3 months, ALN produced a significantly greater mean reduction in urine NTx than did RIS (−52% vs −32%, p < 0.001), which was maintained at 12 months. ALN produced a significantly greater mean BMD increase than did RIS at 6 months, and it was maintained at 12 months at the lumbar spine (4.8% vs 2.8%, p < 0.001) and total hip (2.7% vs 0.9%, p < 0.001), as well as at the trochanter and femoral neck. Significant reductions in BSAP with ALN compared to RIS were maintained over the 12 months of treatment. Study size did not allow for meaningful assessment of differences in fracture rates. Tolerability was generally similar between ALN, RIS and PBO, and the incidence of upper GIAEs causing discontinuation and oesophageal AEs was similar in the ALN and RIS groups.
Conclusion: In this study, ALN 70 mg OW produced a 50% greater reduction in bone resorption as measured by urine NTx and significantly greater increases in lumbar spine and hip BMD than did RIS 5 mg daily. The treatments had similar safety profiles and were generally well-tolerated. Additional studies are needed comparing OW ALN with OW RIS, which became available after the commencement of the present study.
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