Protelos® significantly reduces hip fracture risk in osteoporotic postmenopausal women, Laboratoires Servier

(2005-05-05)

Results of a major new study, published on-line today in the Journal of Clinical Endocrinology and Metabolism, show that a novel treatment for osteoporosis, Protelos® (S12911, strontium ranelate), significantly reduces the risk of hip fractures in osteoporotic postmenopausal women.

Protelos® information for health care professionals.

The TReatment Of Peripheral OSteoporosis (TROPOS) study, a large international randomised, placebo-controlled clinical trial, found that Protelos® reduced the risk of hip fractures, the most debilitating form of fracture, by 36 per cent (P=0.046) in postmenopausal osteoporotic women over a three-year period. Protelos® also significantly reduced the risk of all peripheral fractures and major peripheral fractures. The TROPOS study also confirmed the efficacy of Protelos® against new vertebral fracture shown in a previous phase III study.2 In addition it demonstrated that Protelos® is effective in less severe patients (those without previous vertebral fractures) reducing their risk of vertebral fracture by 45 per cent over 3 years (P<0.001).

Protelos® has been recently licensed across Europe in the treatment of postmeonopausal osteoporosis to reduce the risk of vertebral and hip fractures.4 It is the first agent of its kind with a dual action on bone metabolism, simultaneously increasing bone formation and decreasing bone resorption.3 This action rebalances bone turnover in favour of the formation of new and strong bone.4,5

The TROPOS study was carried out in 5091 Caucasian women over 74 years of age with a low femoral neck bone mineral density (BMD) T-score. Patients were recruited from 75 trial centers across 12 different countries (Australia, Belgium, Denmark, France, Germany, Greece, Hungary, Italy, Poland, Spain, Switzerland, and the UK). Patients received 2g daily of Protelos® or placebo for the three years.

Protelos® was reported to be well tolerated, with no differences in the incidence of serious adverse events between groups. Protelos® was particularly well tolerated at the upper gastrointestinal level.

Publication of the TROPOS results shows that Protelos® is effective against the most debilitating kind of fractures, hip fractures, and confirms that its is well-tolerated and easy-to-take treatment for postmenopausal women with osteoporosis. These results combined with its unique dual mode of action and previously published results on efficacy against vertebral fractures, place Protelos® as a first-line treatment for postmenopausal osteoporosis. This new approach to treating osteoporosis offers doctors and patients alike new hope in the fight against osteoporosis.

Protelos® information for health care professionals.

References:

1 - Reginster JY, Seeman E, De Vernejoul, et al. Strontium ranelate reduces the risk of nonvertebral fractures in post-menopausal women with osteoporosis:TROPOS Study . JCEM Rapid Electronic Publication. February 2005.

2 - Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med.2004;350:459-468.

3 - Marie PJ, Ammann P, Boivin G, et al. Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int. 2001;69:121-129.

4 - European Summary of Product Characteristics.

5 - Ammann P, Shen V, Robin B, et al. Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats.J Bone Miner Res 2004;19 (12). 2012-2020.

OSTEOPOROSIS
BACKGROUND INFORMATION

Osteoporosis is a bone disease characterized by bone fragility due to low bone mass and changes in internal bone structure. This results in an increase in the susceptibility to fractures occurring after minor trauma. Osteoporosis primarily affects women.

What causes osteoporosis?

Human bone is constantly undergoing a remodeling process, in which bone is removed and reformed. Two types of cells mediate this process; osteoblasts are responsible for creating the bone matrix and mineralizing bone, and osteoclasts for resorbing bone. However, if the body begins to resorb bone faster than new bone is produced then over a period of time there is a decrease in bone mass and osteoporosis occurs.

Following the menopause, there is an oestrogen deficiency as a result of a loss of oestrogen production by the ovaries, which is associated with an increased rate of bone turnover and an accelerated rate of bone loss [1]. This accelerated bone loss induces a decrease in bone mass and an increased incidence of fractures [2].

How common is osteoporosis?

It is difficult to assess the prevalence of osteoporosis because the majority of osteoporosis cases are undiagnosed [3]. Although osteoporosis can strike at any age, the incidence of fractures increases exponentially with age. About 40% of women aged 50 years are predicted to sustain at least one fracture in the remainder of lifetime, of whom 20% are expected to suffer from multiple fractures [4].

Hip fractures

The incidence of hip fractures rises exponentially with age in most parts of the world [5] with the incidence rising dramatically around 74 years of age [6]. Most hip fractures result from a fall from standing height (or lower) in women with low bone strength [7]. Aging increases the number of falls, which are caused by slipping or stumbling and loss of balance; furthermore, women experience more falls than men [8].

Hip fractures are associated with an overall mortality of 15% to 30%, most of the excess deaths occurring within the first 6 months after the fracture [9]. Hip fractures are associated with high morbidity requiring a mean hospital stay of 20 to 30 days, and more than 30% of women who have had a hip fracture loose their independence. The number of hip fractures worldwide are projected to increase almost fourfold from 1990 to 2050.

Vertebral fractures

Unlike hip fractures, vertebral fractures are difficult to diagnose. Seventy-five per cent of vertebral fractures occur without any trauma, after an everyday action such as bending or getting up, with less than a quarter resulting from falls. The majority of vertebral fractures are asymptomatic, and remain undiagnosed. Vertebral fractures produce serious consequences, such as long-term pain, deformities, loss of height, and related physical disability, and have a considerable impact on quality of life. Although many fractures occur without any pain, substantial back deformities can lead not only to functional difficulties but also to psychological concerns such as loss of self-esteem and depressive states.

References:

1 - Parfitt AM. Age-related structural changes in trabecular and cortical bone: Cellular mechanisms and biochemical consequences. Calcif Tissue Int. 1984;36:S123-S128.

2 - Riggs BL, Melton III LJ. Involutional osteoporosis. N Engl J Med. 1998;314:1676-1686.

3 - Norman P. Outlook for the osteoporosis market to 2005. SPECTRUM therapy markets and emerging technologies. Decision Resources; 2001.

4 - Doherty DA, Sanders KM, Kotowicz MA, Prince RL. Lifetime and five-year age-specific risks of first and subsequent osteoporotic fractures in postmenopausal women. Osteoporos Int. 2001;12:16-23.

5 - Johnell O, Gullberg B, Allander E, Kanis JA. The apparent incidence of hip fracture in Europe: a study of national register sources. MEDOS Study Group. Osteoporos Int. 1992; 2:298-302.

6 - Donaldson LJ, Cook A, Thomson RG, et al. Incidence of fractures in a geographically defined population. J Epidemiol Community Health. 1990;44:241-245

7 - Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761-7.

8 - Cooper C. Epidemiology of osteoporosis. Osteoporos Int. 1999; 9(Suppl 2):S2-8.

9 - Report on osteoporosis in the European Community. Action for prevention. European Communities, 1998.

Protelos® information for health care professionals.

For further information, please contact:
Stéphanie Makin
Tonic Life Communications
Tel: +44 20 7798 9905
E-mail: stephanie.makin@toniclc.com