Better bone health for osteoporotic patients: Protelos decreases fracture risk and improves bone quality




Philippe HALBOUT, PhD
Servier International
Suresnes, FRANCE

Better bone health for osteoporotic patients: Protelos decreases fracture risk and improves bone quality

by P. Halbout , France

Estrogen depletion in postmenopausal women induces a rapid decrease in bone quality, bone quantity, and consequently, bone strength, resulting in an increase in fracture risk. Treatments addressing osteoporosis must be judged not only on their ability to decrease the risk of fractures, but also to improve the bone status of osteoporotic women and ensure efficacy and long-term protection, whatever the patient profile, including those patients most difficult to treat. Protelos (strontium ranelate) is an antiosteoporotic agent indicated in the prevention of vertebral and hip fracture risk in postmenopausal women with osteoporosis. The efficacy of Protelos actually goes beyond this definition inasmuch as its range of efficacy extends from preventing fracture risk in osteopenic patients to those with the most severe forms of osteoporosis, and from the youngest patients to those most advanced in years. Protelos is the only among all other antiosteoporotic agents with proven long-term efficacy against vertebral, nonvertebral, and hip fractures over 5 years, as established by a randomized, double-blind controlled trial. This efficacy is acknowledged by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), which published, in 2008, a European Guidance that ranked Protelos as a first-line treatment with proven efficacy in reducing the risk, not only of vertebral fractures, but also of nonvertebral fractures, among which specifically hip fractures. Protelos’s unrivalled efficacy results from its ability to build new bone and improve bone health in osteoporotic women. Three studies have shown that Protelos consistently improves both cortical and trabecular bone, which are the main determinants of hip and vertebral fractures, respectively. In osteoporotic women, the improvement in bone architecture with Protelos is already significant after 1 year of treatment and ismaintained over 5 years. Protelos builds strong and healthy bone and provides full protection against fracture risk in osteoporotic postmenopausal women. Protelos heralds a new therapeutic approach that fills the bill as first-line treatment in the management of osteoporosis.

Medicographia. 2010;32:408-416 (see French abstract on page 416)

The changes that take place at bone tissue level in postmenopausal women lead to a decrease in both quantity and quality of bone. These changes dramatically decrease bone strength while silently increasing the risk of fractures. The main goal of the first-generation drugs that were designed to treat osteoporosis— like the antiresorptives developed 40 years ago—was basically to prevent the risk of fractures by stopping the degradation of bone. Unfortunately, this strate- gy was not effective enough to ensure a satisfactory outcome of the management of osteoporosis. First, these agents failed to provide complete efficacy in preventing hip and vertebral fractures; second, they proved unable to build new bone to counterbalance the bone loss induced by the menopause; third, their efficacy over the entire range of osteoporosis patient profiles and in the long-term is not established; fourth, these drugs stop bone remodeling, an effect that may be associated with rare, but severe, side effects on bone.

Today’s treatment of osteoporosis must aim to improve bone architecture while taking into account the living nature of bone tissue; this is particularly crucial in view of the long-term nature of osteoporosis treatment. Protelos is a modern treatment for postmenopausal osteoporosis with proven efficacy against vertebral and hip fractures, whatever the risk factors, both in the short and in the long-term. The antifracture efficacy of Protelos has direct benefits for bone architecture: there is robust evidence showing that, thanks to its unique dual mode of action, Protelos builds strong and healthy bone in postmenopausal osteoporotic women. This chapter focuses on Protelos’ ability to ensure comprehensive antifracture efficacy against all types of osteoporotic fractures, while at the same time improving bone health in osteoporotic patients (Figure 1).

Figure 1
Figure 1. Key criteria for the treatment of osteoporosis.

Comprehensive efficacy: Protelos protects against vertebral, nonvertebral, and hip fractures

Two types of fractures must be considered in the prevention of fractures in postmenopausal women with osteoporosis:
_ Vertebral fractures: these are themost common type of fracture, which generally occur in the youngest osteoporotic patients; when associated with height loss or back pain they are designated as “clinical vertebral fractures”;
_ Hip fractures: these are definitely the most serious type of fracture and have a major impact on morbidity and mortality, especially in elderly subjects.

Two pivotal trials have assessed the efficacy of Protelos: SOTI (the Spinal Osteoporosis Therapeutic Intervention trial) and TROPOS (TReatment Of Peripheral Osteoporosis Study). Both were multinational, randomized, double-blind, and placebocontrolled trials, involving a total of 6740 postmenopausal women, all of whom received concomitant calcium/vitamin D supplementation at a dose tailored to the degree of deficiency (calcium 500/1000 mg; vitamin D3 400/800 IU).

Figure 2
Figure 2. Effects of Protelos on vertebral fracture risk in women
with postmenopausal osteoporosis.

Abbreviations: ARR, absolute risk reduction; CI, confidence interval; RR, relative risk.
Modified after reference 1: Meunier et al. N Engl J Med. 2004;350:459-468.
© 2004, Massachusetts Medical Society.

_ SOTI included 1649 postmenopausal women aged =50 years with =1 vertebral fracture(s) and lumbar spine bonemineral density (BMD) =0.840 g/cm², assessed by means of a Hologic™BMD diagnosis system (www.hologic.com). This trial was designed to assess the efficacy of Protelos against vertebral fractures. Protelos decreased new vertebral fracture risk by 49% after only 1 year (relative risk [RR], 0.51; 95% confi- dence interval [CI], 0.36-0.74; P<0.001). Clinical vertebral fractures, defined as vertebral fracture associated with back pain and/or height loss =1 cm, fell by 52%, also as early as by the first year of treatment (RR, 0.48; 95% CI, 0.29-0.80; P=0.003). Reductions in vertebral and clinical vertebral fractures were still significant at 3 years (41%; RR, 0.59; 95% CI, 0.48-0.73, and 38%; RR, 0.62; 95% CI, 0.47-0.83, respectively, both P<0.001) (Figure 2, page 409).1

_ TROPOS assessed the efficacy of Protelos against nonvertebral and hip fractures in 5091 postmenopausal women with femoral neck BMD equivalent to a T-score below –2.5 SD (centralized normative data analysis: Dr D. O. Slosman, Geneva, Switzerland), and age =74 years or 70 to 74 years with an additional fracture risk factor. At 3 years, Protelos decreased the risk of nonvertebral fractures by 16% (RR, 0.84; 95% CI, 0.702-0.995; P<0.05) and the risk of major nonvertebral fractures (hip, wrist, pelvis, sacrum, ribs-sternum, clavicle, and humerus) by 19% (RR, 0.81; 95% CI, 0.66-0.98; P<0.05) (Figure 3).2 In the subgroup of patients with the highest risk of hip fracture, ie, those aged =74 years with femoral neck T score =–3 SD, Protelos decreased the risk of hip fractures by 36% (RR, 0.64; 95% CI, 0.412-0.667; P=0.046) over 3 years. TROPOS also confirmed the decrease in risk of new vertebral fractures over 1 and 3 years by 45% (RR, 0.55; 95% CI, 0.39-0.77; P<0.001) and 39% (RR, 0.61; 95% CI, 0.51-0.73; P<0.001), respectively, versus placebo. In summary, SOTI and TROPOS confirmed the efficacy of Protelos against all types of osteoporotic fractures, including vertebral and hip fractures, and thus its comprehensive efficacy in postmenopausal women.3

Figure 3
Figure 3. Decrease in relative risk of nonvertebral and major nonvertebral
fractures with Protelos vs placebo in the TROPOS study.

Abbreviations: ARR, absolute risk reduction; BMD, bone mineral density; CI, confidence interval; RR, relative risk; TROPOS, TRreatment Of Peripheral Osteoporosis Study.
Modified after reference 2: Reginster et al. J Clin Endocrinol Metab. 2005;
90:2816-2822. © 2005, The Endocrine Society.

Place of Protelos in the treatment of osteoporosis

For clinicians treating patients with osteoporosis, it is difficult to judge the comparative efficacy of antiosteoporotic treatments due to the fact that no comparative studies are available. This is because such studies are in practice not feasible, as they require an exceedingly high number of patients and long-term follow-up. In an attempt to obviate this difficulty, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published in 2008 the European Guidance for the Treatment and Management of Osteoporosis in Postmenopausal Women, which compared the efficacy of antiosteoporotic treatments on the basis of the findings of available large trials. In Table 6 of the Guidance, the board of experts highlights the efficacy of Protelos against vertebral and nonvertebral—including hip—fractures in patients with osteoporosis and established osteoporosis, in comparison with other treatments (Table I).4

Table I
Table I. Protelos is the only treatment with demonstrated efficacy against vertebral, nonvertebral, and hip fractures, whatever the severity of osteoporosis.

Abbreviations: HRT, hormone replacement therapy; NA, no evidence available; PTH, parathyroid hormone. Adapted from reference 4: Kanis et al. Osteoporos Int. 2008;19:399-428. © 2008, Springer London.

Full assessment of efficacy requires that the usual analysis of clinical trials and relative risk reduction (RRR) be complemented by the analysis of absolute risk reduction (ARR) and num- ber needed to treat (NNT, the reciprocal of ARR).5 Even if it is not possible to directly compare studies with different populations and different levels of risk, these parameters are fair indicators of the magnitude of the benefits a physician can expect from a treatment. In a very recent review, J. D. Ringe and J. G. Doherty showed that Protelos had very low NNTs, with only 9 patients needing to be treated in order to prevent, over 3 years, 1 vertebral fracture, vs 21 for ibandronate, and 48 patients needed to be treated to prevent 1 hip fracture, vs 91 for three of the bisphosphonates studied by the authors (Figure 4).6 These AAR and NNT figures confirm Protelos as a very effective treatment, and fully justify the ESCEO Guidance ranking Protelos as firstline treatment.

Protelos: efficacy whatever the risk factor profile and whatever the type of patient

Until recently, evaluation of risk of fracture in postmenopausal women was solely based on BMD measurement, with osteopenia being defined by a T-score between –1 SD and 2.5 SD, and osteoporosis by a T-score <–2.5 SD. However, epidemiological studies stress the key role played by other risk factors, the most important one being age, followed by prevalent fractures, steroid treatment, smoking, alcohol intake, maternal fracture history, and low body mass index (BMI).

The diversity of possible risk factor combination profiles makes each osteoporotic patient unique. An ideal treatment should be able to achieve antifracture efficacy independently of any given risk factor profile. This has been widely demonstrated to be the case with Protelos, well before the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX®) to predict fracture risk came into widespread use.

_ Protelos is effective from the youngest to the oldest and frailest osteoporotic patients
In the youngest age-group of postmenopausal women, ie, those aged 50-65 years, in whom osteoporosis, due to a dramatic increase in bone remodeling, is one of the most common disorders, Roux et al showed that Protelos reduced vertebral fracture risk by 43% (RR, 0.57; 95% CI, 0.36-0.92; P=0.019) over 3 years and that this effect was sustained over a further year, as shown by a 35% reduction in vertebral fracture risk at 4 years (RR, 0.65; 95%CI, 0.42-0.99; P=0.049).7 Efficacy was also independent of age in the pooled SOTI and TROPOS populations: 3-year vertebral fracture risk fell by 37% in women <70 years (RR, 0.63; 95% CI, 0.46- 0.85; P=0.003) and by 42%in those aged 70 to 80 years (RR, 0.58; 95% CI, 0.48-0.68; P<0.001).8

Elderly osteoporotic women (80 years and more), because of the frequent combination of risk factors observed in that agegroup, are especially prone to fractures. In these women, osteoporotic fractures have particularly debilitating consequences, characterized by delayed fracture healing, functional impairment, and loss of autonomy.

Figure 4
Figure 4. Efficacy of antiosteoporotic treatments on vertebral (A) and hip (B) fractures.

Abbreviations: ARR, absolute risk reduction; NA not available; NNT, number to treat.
Modified after reference 6: Ringe and Doherty. Rheumatol Int. 2010;30:863-869. © 2010, Springer.

This results in increased mortality and consumption of nursing home and health care financial resources. In such patients, Protelos has been shown to have complete and sustained efficacy, reducing vertebral fracture risk by 59% (RR, 0.41; 95% CI, 0.22-0.75; P=0.002), clinical fractures by 37% (RR, 0.63; 95% CI, 0.44-0.91; P=0.012), and nonvertebral fractures by 41%(RR, 0.59; 95%CI, 0.37-0.95; P=0.027) after 1 year, and by 32% (RR, 0.68; 95% CI, 0.50-0.92; P=0.013), 22% (RR, 0.78; 95% CI, 0.61-0.99; P=0.040), and 31% (RR, 0.69; 95% CI, 0.52-0.92; P=0.011) after 3 years.9 Protelos is the only antiosteoporosis agent to have shown long-term efficacy in the elderly, with decreases of 31% in vertebral fracture risk (RR, 0.69; 95% CI, 0.52-0.92; P=0.010) and 26% in nonvertebral fracture risk (RR, 0.74; 95% CI, 0.57-0.95; P=0.019) over 5 years (Figure 5).10

Figure 5
Figure 5. Decrease in nonvertebral fracture risk in elderly patients
with Protelos.

Abbreviations: ARR, absolute risk reduction; CI, confidence interval; RR, relative risk; SOTI, Spinal Osteoporosis Therapeutic Intervention; TROPOS, TRreatment Of Peripheral Osteoporosis Study.
Modified after reference 10: Seeman et al. Bone. 2010;46:1038-1042. © 2010,
IBMS, International Bone Mineral Society/Elsevier.

A new approach, taking into account not only age, but a combination of health status factors (decreased strength, tiredness, involuntary weight loss, slowness, and inactivity), has recently been used to define the “frailty” of the most elderly patients and analyze the efficacy of antiosteoporotic treatments.11 It was found that frail osteoporotic women were more vulnerable when exposed to stressors and more likely not only to fall, but also, as a result, to fracture. Another finding was that Protelos was shown to be the only treatment able to decrease vertebral fracture risk by 66% (RR, 0.34; 95% CI, 0.12-0.92; P=0.02) and by 58% (RR, 0.42; 95% CI, 0.23- 0.73; P=0.002) over 1 and 3 years, respectively.12

The above confirms that Protelos has complete antifracture efficacy, from the youngest to the most elderly patients. In the youngest patients, the earlier Protelos is introduced at menopause onset, the greater the anticipated benefit. In the oldest patients, clinical trials show a significant reduction in osteoporotic fractures after only 1 year of treatment, indicating that it is never too late to prevent fractures in such patients.

_ Protelos: proven efficacy whatever the type of patient
In osteoporotic women with a hip/lumbar spine T-score is ≤–2.5 SD, Protelos decreases vertebral fracture risk by 39% (RR, 0.61; 95% CI, 0.53-0.70; P<0.001).8 Importantly, this decrease is observed whatever the patient’s risk factor profile. In addition, Protelos is the only treatment able to achieve a reduction in vertebral fracture risk in osteopenic women (hip/ lumbar spine T-score between –1 and –2.5 SD) by as high as 72% (RR, 0.28; 95% CI, 0.07-0.99; P=0.045).13 The efficacy of Protelos is also independent of the number of prevalent fractures: in osteoporotic women with 0, 1, or 2 prevalent fractures, Protelos decreased vertebral fracture risk by 48% (RR, 0.52; 95%CI, 0.40-0.67; P<0.001), 45%(RR, 0.55; 95% CI, 0.41-0.74; P<0.001), and 33% (RR, 0.67; 95% CI, 0.55- 0.81; P<0.001), respectively.8 Similarly, in osteopenic women with and without prevalent fractures, Protelos decreased vertebral fracture risk by 38% (RR, 0.62; 95% CI, 0.44-0.88; P=0.008) and 59% (RR, 0.41; 95% CI, 0.17-0.99; P=0.039), respectively.13

With regard to bone markers, Protelos decreased vertebral fracture risk by 33% (RR, 0.67; 95% CI, 0.47-0.95; P=0.023) and 49% (RR, 0.51; 95% CI, 0.37-0.70; P<0.001) in postmenopausal osteoporotic women with low- and high-turnover, respectively.14

Finally, the efficacy of Protelos has been shown to be independent of family history of osteoporosis, bone mass index, and smoking.8

Figure 6
Figure 6. Decrease in hip fracture risk with Protelos. Results at 3
and 5 years.

Abbreviations: ARR, absolute risk reduction; BMD, bone mineral density; CI, confidence interval; RR, relative risk; TROPOS, TRreatment Of Peripheral Osteoporosis Study.
Modified after reference 15: Reginster et al. Osteoporos Int. 2008;1(suppl 1):
S26-S27. (Abstract OC49; ECCEO 2008).© 2008, Springer London.

Protelos: comprehensive efficacy over 5 years, sustained over 8 years

In Western societies, in which life expectancy is growing year after year, only an antiosteoporotic treatment with long-term efficacy will be able to guarantee effective protection against the consequences of osteoporotic fractures and preserve the patients’ quality of life. To date, there is no evidence showing that conventional antiosteoporotic treatments, even the bisphosphonates, are able to decrease vertebral or nonvertebral fractures beyond 3 to 4 years of treatment, probably because these treatments fail to create a new and healthy bone in osteoporotic patients. In contrast, Protelos has robust evidence derived from studies with the most stringent design (randomized, double-blind, placebo-controlled trials) that it is effective against vertebral, nonvertebral, and hip fractures over 5 years. This efficacy was even shown to persist after 8 years of treatment, as demonstrated in an open-label extension study of TROPOS.

Randomized, double-blind, multicenter, placebo- controlled studies with a preplanned analysis are the gold standard to assess the efficacy of a treatment: to date, Protelos is the only antiosteoporotic treatment for which long-term efficacy has actually been investigated in such a trial, namely, TROPOS, which was conducted over 5 years. In this trial, Protelos was found to have comprehensive efficacy: nonvertebral fracture risk was reduced by 15% (RR, 0.85; 95% CI, 0.73- 0.99; P=0.032); new major nonvertebral osteoporotic fracture risk was reduced by 18% (RR, 0.82; 95% CI, 0.69-0.98; P=0.025), and vertebral fracture risk was reduced by 24%(RR, 0.76; 95%CI, 0.65-0.88; P<0.001) versus placebo, over 5 years.

In a subgroup of patients at high risk of hip fractures (n=1128; ≥74 years and lumbar/ femoral neck T-score ≤–2.4 SD), Protelos reduced hip fracture risk by 43%versus placebo over 5 years (RR, 0.57; 95% CI, 0.33-0.97; P=0.036) (Figure 6).15 Finally, only 21 patients needed to be treated with Protelos to prevent 1 new osteoporotic fracture.15 The long-term efficacy of Protelos was confirmed in a 3-year open-label extension of TROPOS, including 893 patients followed for a total of 8 years. Cumulative incidence of new vertebral fractures over the 3-year extension period (13.7%, 5-8 years) was fully comparable with that in the first 3 years of TROPOS (11.5%, 1-3 years), thus showing that Protelos’ efficacy extended for as long as over 8 years. The same conclusion can be drawn for nonvertebral fractures, for which the cumulative incidence was similar at the beginning (12%, 1-3 years) and at the end (9.6%, 5-8 years) of the 8-year follow-up of the patients treated with Protelos. Last but not least, assessment of the long-term safety of Protelos showed that it was safe and very well tolerated.16

Protelos treats osteoporosis by building new strong and healthy bone

Although mandatory, it is not enough for an antiosteoporotic treatment today to merely prevent osteoporotic fractures: it should also, concomitantly, be able to treat osteoporotic bone itself. Indeed, since it is the decrease in bone quantity and quality occurring after menopause that is at the origin of the fracture risk in osteoporotic patients, improving bone status is a strong requirement, as only this can ensure strong and rapid protection against all osteoporotic fractures, both in the short and long term. Conventional treatments, including antiresorptive treatments, have not been able to prevent fracture risk in the long term, nor have they shown effectiveness in patients displaying the most severe risk factor profiles, probably due to the fact that these treatments are unable to build new bone. It is now well established that the increase in BMD observed in bisphosphonate-treated patients is due to the hypermineralization of bone resulting from the marked decrease in bone remodeling induced by these agents. The consequence of this negative impact on bone remodeling is illustrated by the rare—but dangerous—occurrence of severe side effects on bone leading to atypical fractures—an issue of growing concern for the European Medicines Agency (EMA) and US Food and Drug Administration (FDA). The situation is quite the reverse with Protelos. Protelos provides a new approach to the management of osteoporosis thanks to its unique dual mode of action, which enables it to build new and strong bone (Figure 7, page 413).17,18 It shows comprehensive and long-term efficacy whatever the type of osteoporotic fracture, whatever the patient’s profile, and whatever the patient’s risk factors. With Protelos, it is now possible not only to prevent fractures, but also to treat osteoporotic bone, as consistently confirmed in the literature.

Figure 7
Figure 7. The unique mode of action of Protelos.

Protelos increases bone formation through an increase in osteoblast replication, differentiation, and activity. In parallel, Protelos decreases bone resorption via a decrease in osteoclast differentiation and activity and the upregulation of the OPG/RANKL ratio in osteoblasts.
Abbreviations: CaSR, calcium-sensing receptor; OPG, osteoprotegerin; RANK(L), receptor activator nuclear factor-?B (ligand).
Modified after references 17 and 18: Marie et al. Calcif Tissue Int. 2001;69(3):121-129. © 2001, Springer; and Brennan et al. Calcif Tissue Int. 2006:78:S129 (Abstract P356). © 2006, Springer.

Bone biopsies from SOTI and TROPOS patients were the first to establish the efficacy of Protelos in osteoporotic patients. Treatment for 3 years resulted in marked bone microarchitecture benefits, as evidenced by an 18% increase in cortical bone thickness (P=0.008) and a 14% increase in trabecular number (P=0.05), together with a 16% decrease in trabecular separation (P=0.004). These beneficial effects of Protelos on bone architecture result from increased osteoblast activity, as reflected by an increase in mineral apposition rate (+9%; P=0.019) and osteoblast surface (+38%; P=0.047), and a 10% trend toward a decrease in osteoclast surface. These improvements were associated with a change in bone structure from “rod-like” on placebo to “plate-like” on Protelos, signaling more resistant bone (Figure 8).19

Further demonstration is provided by a comparison of the effects of Protelos and alendronate in a recent head-to-head randomized, double-dummy, double-blind study in osteoporotic women.20 In this study, a high-resolution-peripheral quantitative computed tomography (HR-pQCT, SCANCO Medical) was used to compare the effect on bone microarchitecture after 1 year of treatment with Protelos versus alendronate. Results showed that cortical thickness was increased by 5.3% (P<0.001) and trabecular bone volume/tissue volume ratio by 2.0% (P=0.002) with Protelos; the changes in each parameter were significant as early as by 3 months of treatment (P=0.012 and P=0.042, respectively) (Figure 9); and remained so after 2 years.21 No improvement occurred in the alendronate group, confirming alendronate’s inability to build new bone.20

Figure 8
Figure 8. Improvement in bone architecture at cortical and trabecular
sites in postmenopausal women with osteoporosis with
Protelos.

Modified after reference 19: Arlot et al. J Bone Miner Res. 2008;23:215-222.
© 2008, ASBMR, The American Society for Bone and Mineral Research.

Figure 9
Figure 9. Comparison of changes in cortical thickness and ratio of bone volume to tissue volume for Protelos and alendronate.

Abbreviations: Ct.Th, cortical thickness; BV/TV, bone volume/tissue volume.
Modified after reference 20: Rizzoli et al. Rhumatol Int. 2010;30:1341-
1348. © 2010, Springer.

Analysis of hip architecture in TROPOS patients is yet another demonstration of the benefits of Protelos on bone. The relationship between hip geometry and bone strength was studied in 483 TROPOS patients (Protelos, n=251; placebo, n=231) after 5 years of treatment, by using the dual-energy x-ray absorptiometry (DXA)-derived hip structure analysis (HSA) program devised by Thomas Beck. In this study, Protelos was shown to increase cortical thickness at the femoral neck, intertrochanteric region, and proximal shaft (+5.2±9.8% vs –3.6±7.9%, P<0.001 vs placebo). This improvement in bone microarchitecture was independent of the increase in BMD and resulted in improved bending strength, with an increase in section modulus of +8.6±14.3% vs –2.3±11.6% vs placebo (P<0.001; Figure 10).22

Finally, four recent studies performed in nonclinical models— including osteoporotic models—have shown that the effects of Protelos on bone architecture improved fracture healing and osseointegration. Thus, Ly et al23 and Haberman et al24 evidenced a consistent improvement in both bone callus architecture and bone strength with Protelos, but not with teriparatide. In parallel, two other studies25,26 showed that treatment with Protelos improved osseointegration by increasing the resistance of implants in bone.

In summary, three independent clinical studies have consistently demonstrated the benefits of Protelos on bone in postmenopausal osteoporotic patients. The improvement in cortical bone—which is the main determinant of hip fracture—is undoubtedly the basis for Protelos’ efficacy in reducing the risk of hip fractures, while the efficacy of Protelos in improving trabecular bone—which is the main determinant of vertebral fracture—accounts for its ability to reduce the risk of vertebral fractures. Importantly, these studies also illustrate the consistency of the relationship between the improvement in bone health with Protelos, which has been established by randomized clinical trials after 1, 3, and 5 years of treatment, and the efficacy of Protelos in decreasing the risk of osteoporotic fractures, likewise established after 1 to 5 years of treatment. The fact that Protelos is able to treat the osteoporotic bone explains its comprehensive efficacy against osteoporotic fractures, whatever the patient profile, whatever the type of fracture, and that this efficacy extends to the long term. Finally, no abnormalities in bone structure or mineralization have been reported after 5 years of treatment with Protelos, indicating that, besides its obvious benefits in terms of bone architecture, Protelos is totally safe for bone, as well as for patients.27

Figure 10
Figure 10. Protelos improves hip geometry and bone strength
compared with the placebo group.

Abbreviations: CSA, cross-sectional area; CSMI, cross-sectional moment of inertia.
Modified after reference 22: Briot et al. Ann Rheum Dis. 2009;68(suppl 3)665.
Abstract SAT0375. © 2009, BMJ Publishing Group.

Conclusion

Consistent and robust evidence supports the efficacy of Protelos in improving cortical and trabecular bone, the main determinants of hip and vertebral fractures, respectively. Protelos treats the bone defects responsible for the increased risk of fractures in postmenopausal women by building new strong and healthy bone. This effect accounts for the comprehensive efficacy of Protelos in reducing vertebral, nonvertebral, and hip fracture risk, no matter what the patient profile. Protelos’ efficacy develops quickly and is sustained in the longterm. Studies consistently show that the efficacy of Protelos is superior to that of other antiosteoporotic agents, both on bone architecture and on reduction of fracture risk. By building strong and healthy bone and providing comprehensive protection against fractures in osteoporotic postmenopausal women, Protelos ushers in a new era as first-line treatment in the management of osteoporosis. _

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Keywords: strontium ranelate; osteoporosis; treatment guidelines; Protelos