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Differences between trial populations used for indirect comparisons between strontium and alendronate. (Additional content — Strontium ranelate (Protos) for postmenopausal osteoporosis.)

  • 2 min read
  • 1 November 2007

 

This page contains additional information about the article Strontium ranelate (Protos) for postmenopausal osteoporosis, published in NPS RADAR, November 2007.

Women enrolled in TROPOS probably had a higher risk of fracture than those in FIT-2 because of the mixture of primary and secondary prevention populations, and the fact that they were older and had lower average BMD (see Table 1). In TROPOS, 55% had a previous fracture, however, only 71% of the whole population were X-rayed for vertebral fracture, hence the exact proportion is unknown. These factors may explain why the absolute risk of fracture differs between TROPOS and FIT-2, as seen by comparing the placebo fracture event rates* (6.4% strontium; 2.2% alendronate). Though not identical, women in SOTI and FIT-1 showed more similarity in baseline fracture risk (see Table 2).14,16

* The validity of an indirect comparison depends on the included trials being similar (assuming each trial is internally valid) because the drug's absolute treatment effects (defined by the absolute risk reduction or number needed to treat) are influenced by baseline risk.
Table 1 Key characteristics of the TROPOS13 and FIT-215 trials (used for primary prevention comparison)

TROPOS FIT-2 (primary prevention)
Baseline risk
  • Femoral neck BMD < 0.60 g/cm2
  • 55% of women had a previous fracture (vertebral or non-vertebral) confirmed by X-ray
  • Mean femoral neck BMD 0.59 g/cm2
  • No previous radiographic vertebral fracture confirmed by X-ray
  • 35% had a history of postmenopausal fracture
Vertebral X-ray before randomising No
 Yes
Number of women 4932 4432
Completed follow-up 3320 (67%) 4134 (93%)
Mean age 77 years 68 years
Study centres 11 European countries and Australia 11 metropolitan areas of the United States
Intervention Strontium (either 2 g once daily or 1 g twice daily) versus placebo for 3 years Alendronate 5 mg daily for 2 years then 10 mg daily versus placebo for 4 years
Primary outcome New non-vertebral fracture (excluding skull, face, finger, toe and coccyx) as diagnosed by a physician One or more clinical fractures — pre-specified as vertebral, non-vertebral, hip, wrist and 'other' (excluding face or skull) as diagnosed by a physician
Secondary outcomes Study not powered for these outcomes Study not powered for this outcome
TROPOS = Treatment of Peripheral Osteoporosis study13
FIT-2 = Fracture Intervention Trial15
Table 2 Key characteristics of the SOTI14 and FIT-116 trials (used for secondary prevention comparison)

SOTI FIT-1 (secondary prevention)
Baseline risk
  • Mean femoral neck BMD 0.59 g/cm2
  • All had vertebral fracture at baseline (confirmed by X-ray)

In addition to one baseline vertebral fracture:

  • Mean of two previous vertebral fractures
  • 33% had a previous non-vertebral fracture
  • Mean femoral neck BMD 0.57 g/cm2
  • All had vertebral fracture at baseline (confirmed by X-ray)

In addition to one baseline vertebral fracture:

  • 31% had multiple vertebral fractures
  • 57% had a history of postmenopausal fracture
  • About 30% had maternal history of fracture and previous falls
Number of women 1442 2027
Completed follow-up 1260 (87%) 1946 (96%)
Mean age 70 years 71 years
Study centres 11 European countries and Australia 11 metropolitan areas of the United States
Intervention Strontium (either 2 g once daily or 1 g twice daily) versus placebo for 3 years Alendronate 5 mg daily for 2 years then 10 mg daily versus placebo for 3 years
Primary outcome New radiographic or clinical vertebral fracture New radiographic vertebral fractures
Secondary outcomes Study not powered for this outcome Study powered for this outcome
SOTI = Spinal Osteoporosis Therapeutic Intervention study14
FIT-1 = Fracture Intervention Trial16
 

 References

References for this article are found on the page Strontium ranelate (Protos) for postmenopausal osteoporosis, from NPS RADAR November 2007.