Unique Paired Biopsy Study Shows Normal Bone Formation After Five Years of Risedronate Treatment

Main Category: Bones / Orthopedics
Article Date: 10 Jun 2004 - 6:00 PDT


New data from a study evaluating paired bone biopsies at the start of and after five years of risedronate (Actonel®/Optinate®) treatment in postmenopausal women with osteoporosis demonstrates that the new bone formed was normal and of good quality. From the biopsies, a moderate suppression of bone remodeling was shown, which was in line with the estimated suppression of turnover assessed by serum bone turnover markers [ostase (-33 percent) and N-telepeptide/creatinine (-47 percent) markers (p ≤0.05)]. The findings of the study were presented today at the annual meeting of the European Calcified Tissues Society (ECTS).

Bone quality is an umbrella term used to describe factors that influence bone strength, and ultimately, fracture resistance. Bone strength depends on structural properties, material properties and bone turnover. Bone turnover (the balanced removal, replacement and microscopic repair of bone tissue) is important because it influences both the structure and the material of bone. Optimal rates of bone turnover may therefore promote stronger bones.

"Strong bones fracture less and getting the bone turnover right, well within the premenopausal range, is important because of its influence on bone strength," said Arkadi Chines, MD, Associate Professor of Clinical Medicine, University of Cincinnati, and Global Medical Director, Procter & Gamble Pharmaceuticals. "There is an emerging consensus that bone strength and the factors that influence it is what really matters in assessing treatments for osteoporosis. This study confirms that risedronate therapy reduces bone turnover to within normal premenopausal range while formation of good quality bone continues even after five years of treatment."

About Osteoporotic Fracture

A disease characterized by low bone mass and microarchitectural deterioration of bone tissue, postmenopausal osteoporosis leads to reduced bone strength and a consequent increase in fracture risk.[i] Fracture is the most detrimental outcome of decreased bone strength because it is associated with high morbidity and mortality, and once a fracture occurs, another may occur within one year.[ii] As a result, the most important goal of osteoporosis treatment is rapid and sustained fracture reduction.[iii]

About the Study

These unique data came from a five-year placebo-controlled paired biopsy study of 86 postmenopausal women with osteoporosis who received either risedronate (44 patients) or placebo (42 patients). Bone tissue biopsies from 21 and 27 patients respectively were taken and histologically assessed at baseline and five years in both treatment groups. The biopsies showed that the new bone formed was normal and of good quality.

A significant moderate and sustained decrease in bone turnover was seen at five years in the risedronate group with no significant decrease in the placebo group. This finding is in line with the reduction in ostase and N-telepeptide/creatinine serum markers for bone turnover (-33 percent and -47 percent, respectively) (p ≤0.05). Cortical thickness decreased in both groups, but the risedronate group decrease was about 3-fold less than the placebo group. Lumbar spine BMD increased 9.2 percent relative to baseline in those patients treated with risedronate compared to no significant change in the placebo group. Bone formation and mineralization were normal as assessed by osteoid thickness, mineral apposition rate, mineralization lag time and wall thickness. These data demonstrate moderate suppression of bone turnover with long-term bone safety of risedronate.

About Risedronate Sodium

Risedronate sodium is a bisphosphonate marketed by the Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and Aventis) and currently approved in 82 countries worldwide. Risedronate 35 mg Once a Week and risedronate 5 mg daily are indicated for the treatment of osteoporosis in postmenopausal women. Risedronate 5 mg also is indicated for the prevention of osteoporosis in postmenopausal women and the management of glucocorticoid-induced osteoporosis (GIO).

Risedronate has been proven to provide fast and sustained fracture reduction in postmenopausal women with established osteoporosis. It has been proven to significantly reduce vertebral fractures in just one year.[iv] A significant reduction in clinical vertebral fractures was seen with risedronate as soon as six months.[v] Risedronate also provides sustained vertebral fracture protection in patients treated for seven years.[vi]

In postmenopausal osteoporosis, a significant deterioration in structural and material properties of trabecular bone can occur. Risedronate prevents deterioration of trabecular microarchitecture, which occurs with high bone turnover, over three years.[vii] Risedronate also has shown some data suggesting a preserving effect on collagen structure and mineral crystallinity up to five years.[viii]

Risedronate 5 mg indications:

-- Treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures.

-- Treatment of established postmenopausal osteoporosis, to reduce the risk of hip fractures.

-- Prevention of osteoporosis in postmenopausal women with increased risk of osteoporosis.

-- To maintain or increase bone mass in postmenopausal women undergoing long-term (more than 3 months), systemic corticosteroid treatment at doses 7.5mg/day prednisone or equivalent.

Risedronate 35 mg Once a Week indications:

-- Treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures.

-- Treatment of established postmenopausal osteoporosis, to reduce the risk of hip fractures.

About The Alliance for Better Bone Health

The Alliance for Better Bone Health was formed by Procter & Gamble and Aventis in May 1997 to promote bone health and disease awareness through numerous activities to support physicians and patients around the globe.

About Procter & Gamble

Procter & Gamble Pharmaceuticals is part of Procter & Gamble Health Care, a division of The Procter & Gamble Company (NYSE: PG) - a $40 billion global leader in the development, manufacturing and marketing of a broad range of consumer goods. In prescription drugs, P&G is focusing in the areas of endocrinology, cardiovascular and musculoskeletal diseases, as well as anti-infective therapies. Some of P&G's leading prescription products include Actonel® (risedronate sodium tablets), Asacol® (mesalamine), and Macrobid® (nitrofurantoin monohydrate macrocrystals).

About Aventis

Aventis is dedicated to treating and preventing disease by discovering and developing innovative prescription drugs and human vaccines. In 2003, Aventis generated sales of € 16.79 billion, invested € 2.86 billion in research and development and employed approximately 69,000 people in its core business. Aventis corporate headquarters are in Strasbourg, France. For more information, please visit: http://www.aventis.com

Aventis Press Release

Statements in this news release containing projections or estimates of revenues, income, earnings per share, capital expenditures, capital structure, or other financial items; plans and objectives relating to future operations, products, or services; future economic performance; or assumptions underlying or relating to any such statements, are forward-looking statements subject to risks and uncertainties. Actual results could differ materially depending on factors such as the timing and effects of regulatory actions, the results of clinical trials, the company's relative success developing and gaining market acceptance for new products, the outcome of significant litigation, and the effectiveness of patent protection. Additional information regarding risks and uncertainties is set forth in the current Annual Report on Form 20-F of Aventis on file with the Securities and Exchange Commission and in the current Annual Report -"Document de Référence"- on file with the "Autorité des marchés financiers" in France.

Pursuant to Article 7 of the COB Regulation no. 2002-04, this press release was transmitted to the Autorité des marchés financiers before its release.

References

[i] WHO Consensus Conference 1994

[ii] Lindsay et al. JAMA 2001; 285: 320-23.

[iii] Consensus Development Conference, JAMA 2001; 285: 785-95.

[iv] Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA. 1999; 282:1344-1352.

[v] Watts NB, Adami S, Chestnut CH. Risedronate reduces the risk of clinical vertebral fractures in just 6 months [abstract]. J Bone Miner Res. 2001; 16 (suppl I):S407. Abstract SU409.

[vi] Sorensen O, Goemare S, Wenderoth D, et al. Sustained effect of risedronate: a 7-year study in postmenopausal women. Calcif Tissue Int. 2003; 72(4):402. Abstract P-275.

[vii] Borah, et al. Bone. 2004; 10:142-151.

[viii] Paschalis EP, Phipps R. Three-Years Treatment with Risedronate Preserves Bone Quality. Presented at 2003 ASMBR Conference.

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