Baseline Glucocorticoid Dose and Bone Mineral Density Response with Teriparatide or Alendronate Therapy in Patients with Glucocorticoid-induced Osteoporosis
ABSTRACT This post-hoc analysis studied the effect of baseline glucocorticoid dose on the 18-month bone mineral density (BMD) response to teriparatide 20 microg/day or alendronate 10 mg/day in 387 patients with glucocorticoid-induced osteoporosis (GIO) from a randomized, double-blind trial.
Lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were measured at baseline and 18 months. Mean baseline glucocorticoid dose was categorized as low (< or = 5 mg/day), medium (> 5 and < 15 mg/day), or high (> or = 15 mg/day).
Baseline LS, FN, and TH BMD were similar between groups, and between glucocorticoid dose categories within each group. LS BMD increases at the low, medium, and high glucocorticoid doses were 8.1%, 6.6%, and 4.6%, respectively, with teriparatide, and 3.6%, 2.8%, and 2.3% with alendronate. Analyzed as a continuous variable, higher glucocorticoid doses had a negative, but non-significant, effect on the percentage increase in LS BMD in both groups. Glucocorticoid dose did not significantly affect FN or TH BMD increases in either group. Across the 3 glucocorticoid dose categories, the overall LS BMD increases were different for both treatments combined (p = 0.033), but the relative differences between the treatment groups were not different (interaction, p = 0.52).
Teriparatide and alendronate increased LS and hip BMD across a range of baseline glucocorticoid doses. LS BMD increases with teriparatide were greater in the low-dose category than in the high-dose category. Overall LS BMD increases were significantly greater with teriparatide compared with alendronate, which may reflect the respective anabolic and antiresorptive mechanisms of action. Clinical Trial Registry Number: NCT00051558.
- SourceAvailable from: John H Krege
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- "PINP response to teriparatide in patients with other chronic medical illnesses has been evaluated. PINP was collected in a randomized, double-blind trial of men and women with glucocorticoid-induced osteoporosis (NCT00051558) [47–49]. These individuals had various baseline conditions for which they were treated with glucocorticoids including rheumatoid arthritis, systemic lupus erythematosis, polymyalgia rheumatica, vasculitis, respiratory disorders, and inflammatory bowel disease. "
ABSTRACT: Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis.Osteoporosis International 03/2014; 25(9). DOI:10.1007/s00198-014-2646-0 · 4.17 Impact Factor
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- "In patients treated with teriparatide, lumbar spine BMD increased by 8.1% in the low-dose group, 6.6% in the medium-dose group, and 4.6% in the high-dose group. This is compared with patients treated with alendronate, whereby the lumbar spine BMD increased by 3.6% in the low-dose group, 2.8% in the medium-dose group, and 2.3% in the high-dose group.37 There was no significant difference in BMD at the femoral neck and total hip in either treatment group for the various glucocorticoid doses. "
ABSTRACT: Glucocorticoids are commonly used in various fields within medicine. One of their most common and clinically significant side effects is glucocorticoid-induced osteoporosis (GIOP). GIOP is a disease leading to progressive decreases in bone mineral density, decreased bone strength, and increased risk of skeletal fractures. GIOP has a significant impact on the morbidity and health-related quality of life of the patients it affects. Glucocorticoids have deleterious effects on bone through promoting osteoblast apoptosis and inhibiting osteoblastogenesis. Teriparatide exerts anabolic effects on bone, so it is understandable why teriparatide is thought to be a rational treatment option. Clinical studies have indicated teriparatide is efficacious in the treatment of GIOP to improve bone mineral density values at the lumbar spine and femoral neck. Some evidence also suggests teriparatide may reduce rates of vertebral fractures in GIOP patients. Overall, this review of the current clinical evidence suggests teriparatide may be an efficacious and promising agent in the treatment of GIOP.Therapeutics and Clinical Risk Management 10/2010; 6:497-503. DOI:10.2147/TCRM.S7776 · 1.47 Impact Factor
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ABSTRACT: A bit-level pipelined 12×12-bit two's-complement multiplier with a 27-bit accumulator has been designed for applications in high-speed digital communication systems. A new quasi n-p domino logic structure has been investigated and adopted in this multiplier-accumulator design. When used in fully-pipelined circuits, this logic structure results in a much shorter propagation delay in comparison with conventional CMOS logic, pseudo-NMOS logic, and even standard n-p domino (NORA) logic. The chip complexity is approximately 10000 transistors, and the die area is 9.3 mm<sup>2</sup> in a 1.25-μ p-well CMOS technology. Based on SPICE simulations using conservative device parameters, the clock speed is projected to be over 150 MHz (i.e. >150 million multiply-accumulate operations per second), and the estimated power-speed ratio is 16 mW/MHzComputers and Communications, 1989. Conference Proceedings., Eighth Annual International Phoenix Conference on; 04/1989