Effects of Teriparatide Versus Alendronate for Treating Glucocorticoid-Induced Osteoporosis Thirty-Six-Month Results of a Randomized, Double-Blind, Controlled Trial

University of Alabama at Birmingham.
Arthritis & Rheumatology (Impact Factor: 7.76). 11/2009; 60(11):3346-55. DOI: 10.1002/art.24879
Source: PubMed

ABSTRACT To compare the bone anabolic drug teriparatide (20 microg/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoid-induced osteoporosis (OP).
This was a 36-month, randomized, double-blind, controlled trial in 428 subjects with OP (ages 22-89 years) who had received > or =5 mg/day of prednisone equivalent for > or =3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety.
Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N-terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C-terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P = 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P = 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001).
Our findings indicate that subjects with glucocorticoid-induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate.

Download full-text


Available from: John H Krege, Sep 26, 2015
53 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "Parathyroid hormone (PTH) drugs such as PTH (1–34) and PTH (1–84) are only approved anabolic agents by the US Food and Drug Administration (FDA) and/or European Union (EU) [9]. PTH drugs increase BMD and decrease vertebral fracture risk in humans compared to the anti-resorptive drugs, ALN and a SERM raloxifene, respectively [10], [11]. However, these protein drugs can be applied by only subcutaneous injection on the daily basis, and relatively expensive. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The Wnt/β-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/β-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT) extract as a Wnt/β-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial osteoblasts without cytotoxicity. In addition, HDT extract increased femoral bone mass without inducing significant weight changes in normal mice. In addition, thickness and area of femoral cortical bone were also significantly increased by the HDT extract. Methyl vanillate (MV), one of the ingredients in HDT, also activated the Wnt/β-catenin pathway and induced osteoblast differentiation in vitro. MV rescued trabecular or cortical femoral bone loss in the ovariectomized mice without inducing any significant weight changes or abnormality in liver tissue when administrated orally. Thus, natural HDT extract and its ingredient MV are potential anabolic agents for treating osteoporosis.
    PLoS ONE 01/2014; 9(1):e85546. DOI:10.1371/journal.pone.0085546 · 3.23 Impact Factor
  • Source
    • "In Ts65Dn mice PTH(1–34) treatment significantly increased bone mass and volume at the highest dose tested (80 ug/kg). PTH stimulated both mineral apposition rate and bone formation rate resulting in increased bone mass, consistent with the reported effects of PTH in the treatment of both post menopausal and glucocorticoid-induced osteoporosis [38], [39], [40]. Interestingly, PTH treatment in both WT and Ts65Dn mice increased bone mass and osteoblastic activity (MAR and BFR) to a similar extent, despite the low BMD and decreased bone turnover status of Ts65Dn mice. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS). Patterns of differences are now being recognized as patients' age and these patterns bring about new opportunities for disease prevention and treatment. Low bone mineral density (BMD) has been reported in many studies of males and females with DS yet the specific effects of trisomy 21 on the skeleton remain poorly defined. Therefore we determined the bone phenotype and measured bone turnover markers in the murine DS model Ts65Dn. Male Ts65Dn DS mice are infertile and display a profound low bone mass phenotype that deteriorates with age. The low bone mass was correlated with significantly decreased osteoblast and osteoclast development, decreased bone biochemical markers, a diminished bone formation rate and reduced mechanical strength. The low bone mass observed in 3 month old Ts65Dn mice was significantly increased after 4 weeks of intermittent PTH treatment. These studies provide novel insight into the cause of the profound bone fragility in DS and identify PTH as a potential anabolic agent in the adult low bone mass DS population.
    PLoS ONE 08/2012; 7(8):e42967. DOI:10.1371/journal.pone.0042967 · 3.23 Impact Factor
Show more