Theoretical Model for the Interpretation of BMD Scans in Patients Stopping Strontium Ranelate Treatment

Abstract

Strontium ranelate is a new treatment for osteoporosis that results in large increases in BMD, much of which is an artefact caused by high bone strontium content. We used clinical trial data and a model of long-term strontium kinetics to estimate the effect of past strontium treatment on future BMD measurements. Introduction:The oral administration of strontium ranelate causes a clinically significant overestimation of BMD because of the high attenuation of X-rays by strontium atoms in bone. As more patients are treated with strontium ranelate, questions will arise about the correct interpretation of their future BMD measurements. We performed a theoretical study to calculate the long-term effect of strontium treatment on BMD and establish the duration of past treatment for which the remaining bone strontium content (BSC) has a negligible effect on BMD. Materials and Methods: The BMD changes measured at the spine and hip during strontium ranelate treatment were interpolated from clinical trial data. The long-term retention of strontium in bone was estimated using the International Commission on Radiological Protection (ICRP) strontium retention function modified for use in postmenopausal women. Estimates of the strontium BMD artefact after treatment has stopped were performed on the assumption that the BSC effect accounts for 75% of the total measured BMD change at 3 years. Results: If 75% of the BMD changes are explained by BSC, in the average patient, 3-year treatment leads to a spine BMD artefact of 11.2%, decreasing to 3.8% 10 years after stopping treatment. The BMD artefacts at the total hip and femoral neck sites are smaller by factors of 0.65 and 0.53, respectively. If pre-and posttherapy BMD measurements are available, these predictions can be tailored to the individual patient. On average, 6-month treatment is required for the spine BMD artefact to exceed 3%, the figure adopted as the maximum BMD change caused by bone strontium that has a negligible effect on scan interpretation. Ten years after stopping treatment, 28 months of treatment are required for the residual BMD artefact to still exceed the 3% threshold. Conclusions: Strontium ranelate treatment lasting for >6 months can affect BMD measurements for many years afterward.

The pathogenesis, diagnosis, investigation and management of osteoporosis

“…However, its mechanism of action is not fully understood, and it is likely that its antifracture efficacy is mediated by its effects on bone material properties rather than its rather weak effect on skeletal remodelling 85. A meta-analysis of four trials concluded that there is reasonable evidence strontium ranelate is effective for reducing the risk of vertebral fractures and, to a lesser extent, non-vertebral fractures in women 86.…”

Glucocorticoid-induced osteoporosis: an overview

“…There are no prospective data on the effects of strontium ranelate in GIOP, but a retrospective analysis of its use among a subgroup of chronically GC-treated patients suggested an even greater BMD increase compared with that among risedronate users [98]. Strontium ranelate causes a clinically significant overestimation of BMD because of the high attenuation of x-rays by strontium atoms in bone, compromising the correct interpretation of future BMD measurements [99].…”

Pharmacological Treatment of Osteoporosis

“…It is easier and almost accurate to calculate that half of the DMO gained in the first year of treatment with strontium ranelate is due to an increase on BMD and the rest is due to the higher molecular weight on strontium measured by the DXA. (Blake & Fogelman, 2006b) Currently we have data from clinical studies comparing strontium ranelate to placebo for fracture prevention for up to five years. Moreover we have data of fracture incidence in patients treated with strontium ranelate for up to 10 years.…”