Abstract

The current gold standard for the diagnosis of osteoporosis and the prediction of fracture risk is the measurement of bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA). A low BMD is clearly associated with increased fracture risk, but BMD is not the only determinant of bone strength, particularly in secondary osteoporosis and metabolic bone disorders in which components other than BMD are affected and DXA often underestimates true fracture risk. Material properties of bone which significantly contribute to bone strength have become evaluable in vivo with the impact microindentation (IMI) technique using the OsteoProbe® device. The question arises whether this new tool is of added value in the evaluation of bone fragility. To this effect, we conducted a systematic review of all clinical studies using IMI in vivo in humans also addressing practical aspects of the technique and differences in study design, which may impact outcome. Search data generated 38 studies showing that IMI can identify patients with primary osteoporosis and fractures, patients with secondary osteoporosis due to various underlying systemic disorders, and scarce longitudinal data also show that this tool can detect changes in bone material strength index (BMSi), following bone-modifying therapy including use of corticosteroids. However, this main outcome parameter was not always concordant between studies. This systematic review also identified a number of factors that impact on BMSi outcome. These include subject- and disease-related factors such as the relationship between BMSi and age, geographical region and the presence of fractures, and technique- and operator-related factors. Taken together, findings from this systematic review confirm the added value of IMI for the evaluation and follow-up of elements of bone fragility, particularly in secondary osteoporosis. Notwithstanding, the high variability of BMSi outcome between studies calls for age-dependent reference values, and for the harmonization of study protocols. Prospective multicenter trials using standard operating procedures are required to establish the value of IMI in the prediction of future fracture risk, before this technique is introduced in routine clinical practice.

Highlights

  • Bone fragility is complex and its evaluation represents a significant challenge in clinical practice

  • The tools used to assess bone strength and fracture risk have so far included the measurement of bone mineral density using dual energy x-ray absorptiometry (DXA) and the evaluation of clinical risk factors for increased bone fragility using the FRAX algorithm

  • Evidence has been accumulating about the value of impact microindentation in the in vivo assessment of tissue-level material properties of bone, an important contributor to bone strength in addition to that of bone mineral density (BMD)

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Summary

Introduction

Bone fragility is complex and its evaluation represents a significant challenge in clinical practice. The tools used to assess bone strength and fracture risk have so far included the measurement of bone mineral density using dual energy x-ray absorptiometry (DXA) and the evaluation of clinical risk factors for increased bone fragility using the FRAX algorithm. Other tools more recently included high resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone structure, and finite element analysis (3, 4). These methods are either invasive and time-consuming in their analysis, or associated with high radiation exposure. Material properties of bone, which significantly contribute to bone strength could until recently only be assessed ex vivo on a transiliac bone biopsy specimen. Since the introduction of Reference Point Indentation, the possibility has emerged for directly evaluating tissue-level properties of bone in humans in vivo (5, 6)

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