A Clinical Perspective on Advanced Developments in Bone Biopsy Assessment in Rare Bone Disorders

Abstract

Introduction: Bone biopsies have been obtained for many centuries and are one of the oldest known medical procedures in history. Despite the introduction of new noninvasive radiographic imaging techniques and genetic analyses, bone biopsies are still valuable in the diagnosis of bone diseases. Advanced techniques for the assessment of bone quality in bone biopsies, which have emerged during the last decades, allows in-depth tissue analyses beyond structural changes visible in bone histology. In this review, we give an overview of the application and advantages of the advanced techniques for the analysis of bone biopsies in the clinical setting of various rare metabolic bone diseases. Method: A systematic literature search on rare metabolic bone diseases and analyzing techniques of bone biopsies was performed in PubMed up to 2019 week 34. Results: Advanced techniques for the analysis of bone biopsies were described for rare metabolic bone disorders including Paget's disease of bone, osteogenesis imperfecta, fibrous dysplasia, Fibrodysplasia ossificans progressiva, PLS3 X-linked osteoporosis, Loeys-Diets syndrome, osteopetrosis, Erdheim-Chester disease, and Cherubism. A variety of advanced available analytical techniques were identified that may help to provide additional detail on cellular, structural, and compositional characteristics in rare bone diseases complementing classical histopathology. Discussion: To date, these techniques have only been used in research and not in daily clinical practice. Clinical application of bone quality assessment techniques depends upon several aspects such as availability of the technique in hospitals, the existence of reference data, and a cooperative network of researchers and clinicians. The evaluation of rare metabolic bone disorders requires a repertoire of different methods, owing to their distinct bone tissue characteristics. The broader use of bone material obtained from biopsies could provide much more information about pathophysiology or treatment options and establish bone biopsies as a valuable tool in rare metabolic bone diseases.

Plastin 3 in health and disease: a matter of balance

“…This huge variation in heterozygous women is suggested to be caused by X-inactivation of the mutant allele or PLS3 escaping X-inactivation which is why women are less severely affected [15,126,129,131,132]. Even though bone morphometry was very heterogeneous [16,126,[133][134][135][136], most male patients showed peripheral fractures, low BMD, VCFs, especially in the thoracic spine, and low bone turnover rate, while only a few developed extraskeletal OI traits [108, 126-128, 131, 137-140], developmental delay [15,127] or neuromuscular abnormalities, like waddling gait [108,126,131,141]. So far, no specific biomarkers have been identified, which can distinguish genetic factors of osteoporosis, although microRNAs are getting more and more popular as functional markers [120,142].…”

“…It is well established that PLS3 is highly abundant in the dendrites of osteocytes, which not only control mechanosensing but also regulate osteoblast and osteoclast activity, and an impairment of this cell system might explain the resulting osteoporotic phenotype [136,152]. Indeed, in osteocytes, mutations in PLS3 interfere with cellular signaling, resulting in imbalanced bone homeostasis [121,129].…”

Paget’s Disease of the Bone and Lynch Syndrome: An Exceptional Finding

“…The most important differential diagnosis should be performed with a bone metastasis from her prior malignancy or other unidentified LS-associated cancers. However, at that point, no other cancer was active, and neither relapsed during follow-up [ 92 , 93 , 94 , 95 ].…”