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COMBINATION OF TWO MEDICATIONS HELP POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS

PHILADELPIA – Results from the first large study combining two commonly used osteoporosis treatments suggest that the combination of zoledronic acid and teriparatide could help reduce bone loss in postmenopausal women with osteoporosis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Philadelphia, Pa.

Osteoporosis is a silent disease of the bones that makes them weaken and prone to fracture. By their mid-30s, most people begin to gradually lose bone strength as the balance between losing bone (resorption) and adding new bone (formation) shifts, so that more bone is lost than can be replaced. As a result, bones become thinner and structurally weaker.

Researchers recently studied the effects of a combination of an annual dose of zoledronic acid (Reclast®) and a daily dose of teriparatide (Forteo®) versus either one of the medications alone on the spine and hip bone mass as well as bone loss in 412 postmenopausal women—ages 45 to 87—with osteoporosis.

Researchers place 137 women on the combination therapy, 137 women on zoledronic acid alone, and 138 women on teriparatide alone. Researchers measured changes in the lumbar spine and total hip bone mass at the beginning of the study and at 13, 26 and 52 weeks into the study.

A total of 388 women completed the study. At 52 weeks into the study, lumbar spine bone mass had increased 7.51 percent for women on the combination therapy, 7.05 percent for women on teriparatide alone, and 4.37 percent for women on zoledronic acid alone. The combination therapy also increased lumbar spine mass at weeks 13 and 26 as well as total hip mass at 13, 26 and 52 weeks versus teriparatide alone.

Additionally, blood markers of bone turnover, which may indicate the bone loss associated with osteoporosis, were lower with the combination therapy. Levels of serum C-telopeptide, (commonly called β-CTx) and N-terminal propeptide of type I collagen (commonly called P1NP), were lower among the patients taking the combination therapy than in those on teriparatide alone.

Side effects were noted in 9.5 percent of the combination group, 14.6 percent of those on zoledronic acid alone, and 10.9 percent of those on teriparatide alone. The most frequent side effects found in the combination and zoledronic acid groups (when compared to the teripartide group) were flu-like symptoms.

“The idea of combining a medication that primarily blocks bone breakdown with one that mainly increases bone formation is appealing,” says Kenneth Saag, MD, MSc; Jane Knight Lowe professor of medicine, University of Alabama at Birmingham, and an investigator in the study. “However, past combinations of oral medicines such as alendronate with teriparatide have not encouraged this strategy. This new data suggests that the particular combination of zoledronic acid with teriparatide might be considered for certain high risk patients.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see www.rheumatology.org/annual.

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Editor’s Notes: Dr. Saag will present this research during the ACR Annual Scientific Meeting at the Pennsylvania Convention Center at 2:30 pm  on Sunday, October 18 in Room 112 A. Dr. Saag will be available for media questions and briefing at 1:30 pm on Sunday, October 18 in the on-site press conference room, 109 A.



Presentation Number: 591

Effects of Once-Yearly Zoledronic Acid 5mg in Combination with Teriparatide (PTH) On Postmenopausal Women with Osteoporosis

Cosman Felicia, M, Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY
Kenneth Saag, MD, Department of Medicine, University of Alabama, Birmingham, AL
Erik Eriksen, M, Aker University Hospital, Oslo, Norway, Oslo, Norway
Chris Recknor, M, M.D., United Osteoporosis Centers, Gainesville, FL, USA, Gainesville, FL
Paul Miller, MD, Colorado Center for Bone Research, Lakewood, CO
Susan L. Greenspan, M, M.D., Department of Medicine, University of Pittsburgh, Pittsburgh, PA
Philemon Papanastasiou, PhD, Novartis Pharma AG, Basel, Switzerland
Hanumantha Rao, MSc, Novartis Healthcare Pvt. Ltd, Hyderabad, India
Juerg Gasser , Novartis Pharma AG, Basel, Switzerland
Christina Bucci-Rechtweg, M , Novartis Pharmaceuticals Corp, East Hanover, NJ
Steven Boonen, MD, PhD, University of Leuven, Leuven, Belgium

Purpose: The role of combination therapy with hrPTH (1-34) (PTH) and bisphosphonates (BPs) is unclear and although there does not appear to be an additive effect in terms of bone mineral density, certain BPs may blunt the PTH anabolic effect when administered simultaneously. Zoledronic acid (ZOL) does not blunt the PTH effect in rodent models (Gasser et al. 2006), and we sought to determine the effects in humans of combination therapy with once-yearly i.v ZOL 5mg and daily sc PTH 20mg vs. either agent alone on spine and hip BMD (DXA) and bone turnover markers [serum C-telopeptide, (íŸ-CTx), and N-terminal propeptide of type I collagen, (P1NP)].

Method: This 1-year, partial double-blinded, multicenter study randomized 412 postmenopausal osteoporosis women aged 45–87 yrs, (65±9 yrs) to receive either a combination of ZOL and PTH (n=137), ZOL alone (n=137) or  PTH alone (n=138). Between-treatment comparisons for the percent change in lumbar spine (LS) and total hip BMD relative to baseline were performed at weeks 13, 26 and 52 based on the difference of least square means (LSM) from a two-way ANOVA model including all 3 treatments.

Results: 388 women (94.2%) completed the study. At week 52, the LSM estimates of the percent increase in spine BMD were 7.51%, 7.05%, and 4.37% in the combination arm, PTH and ZOL groups, respectively (NS for combination vs. PTH , p<0.001 for combination and PTH vs. ZOL). The combination therapy significantly increased LS BMD at weeks 13 and 26 and total hip BMD at weeks 13, 26, and 52 vs. PTH alone (all p<0.005) (Figure). In the combination arm, β-CTx declined within 4 weeks and rose progressively thereafter, with levels above baseline within 39 weeks; P1NP increased for up to 4 weeks, declined to a nadir at week 8 and then rose progressively with levels above baseline by week 26. Both β-CTx and P1NP levels were lower with combination arm vs. PTH alone throughout the trial (all p<0.002). Overall incidence of serious adverse events was 9.5%, 14.6 % and 10.9% in combination, ZOL and PTH arms, respectively. Most frequent adverse events in the combination and ZOL arms vs. PTH were transient post-infusion flu-like symptoms.

Conclusion: The concomitant administration of once-yearly i.v ZOL 5mg and daily sc PTH 20mg does not blunt the PTH effect on lumbar spine BMD and results in a significantly greater increment in total hip BMD than PTH alone. Combination therapy could be considered in patients at high risk for hip fracture or those with very low hip BMD.

Figure: Percent change from baseline in lumbar spine BMD (a) and total hip BMD (b) in the treatment groups

Percent change from baseline in lumbar spine BMD (a) and total hip BMD (b) in the treatment groups

Disclosure: C. Felicia, Eli Lilly, Merck, Novartis, Procter & Gamble, NPS Pharmaceuticals, Pfizer, Roche , 5 ; K. Saag, Eli Lilly & Co, Merck, Novartis, Amgen, Roche, Procter & Gamble, and Aventis, 5, Aventis, Eli Lilly & Co, Novartis, Amgen, Roche, TAP, and GlaxoSmithKline, 2 ; E. Eriksen, Novartis, Lilly, Novo-Nordisk, 5 ; C. Recknor, Lilly, Roche, Procter and Gamble, GSK, Merck, Aventis, 5, Lilly, Roche, Procter and Gamble, 6 ; P. Miller, Amgen Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Procter & Gamble Pharmaceuticals, Inc., Roche, and sanofi-aventis , 5, Amgen Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Procter & Gamble Pharmaceuticals, Inc., Roche, and sanofi-aventis., 2 ; S. L. Greenspan, Merck, Proctor & Gamble, Lilly , Novartis, 2, Merck, Amgen , 5 ; P. Papanastasiou, Novartis Pharmaceutical Corporation, 3 ; H. Rao, Novartis Pharmaceutical Corporation, 3 ; J. Gasser, Novartis Pharmaceutical Corporation, 3 ; C. Bucci-Rechtweg, Novartis Pharmaceutical Corporation, 1, Novartis Pharmaceutical Corporation, 3 ; S. Boonen, Novartis Pharmaceutical Corporation, 5, Novartis Pharmaceutical Corporation, 2, Novartis Pharmaceutical Corporation, 8.