Evidence for Ongoing Modeling-Based Bone Formation in Human Femoral Head Trabeculae via Forming Minimodeling Structures: A Study in Patients with Fractures and Arthritis

Abstract

Bone modeling is a biological process of bone formation that adapts bone size and shape to mechanical loads, especially during childhood and adolescence. Bone modeling in cortical bone can be easily detected using sequential radiographic images, while its assessment in trabecular bone is challenging. Here, we performed histomorphometric analysis in 21 bone specimens from biopsies collected during hip arthroplasty, and we proposed the criteria for histologically identifying an active modeling-based bone formation, which we call a “forming minimodeling structure” (FMiS). Evidence of FMiSs was found in 9 of 20 specimens (45%). In histomorphometric analysis, bone volume was significant higher in specimens displaying FMiSs compared with the specimens without these structures (BV/TV, 31.7 ± 10.2 vs. 23.1 ± 3.9%; p < 0.05). Osteoid parameters were raised in FMiS-containing bone specimens (OV/BV, 2.1 ± 1.6 vs. 0.6 ± 0.3%; p < 0.001, OS/BS, 23.6 ± 15.5 vs. 7.6 ± 4.2%; p < 0.001, and O.Th, 7.4 µm ± 2.0 vs. 5.2 ± 1.0; p < 0.05). Our results showed that the modeling-based bone formation on trabecular bone surfaces occurs even during adulthood. As FMiSs can represent histological evidence of modeling-based bone formation, understanding of this physiology in relation to bone homeostasis is crucial.

Modeling-Based Bone Formation in the Human Femoral Neck in Subjects Treated With Denosumab

“…From biopsies in subjects undergoing total hip arthroplasty or femoral head replacement, Sano et al revealed strong histomorphometric evidence of MBBF on trabeculae in loaded femoral heads, even in elderly subjects. (34) Thus, bone in the femoral neck may hold greater potential for modeling because it is weight bearing. Additional studies are needed to address bone histomorphometry and levels of MBBF and RBBF in the femoral neck in the untreated population and those who have been treated with denosumab.…”

Buds of new bone formation within the Femoral Head of Hip Fracture Patients Coincide with Zones of Low Osteocyte Sclerostin

“…2). Note that with respect to a previous study, ( 25 ) we have abandoned the requirement of a relatively lower mineralization based on the fluorescent signal since we now consider the osteoid seam to be sufficient evidence for a state of active modeling. The N.FMiS/T.Ar was averaged over the three separated sections.…”

“…Our histological identification of a FMiS on a trabecular surface does not rely on fluorochrome prelabeling. ( 25 ) Instead, it is defined by the following criteria: the base of the FMiS is a smooth and lamellar BS, the lamellar pattern of the FMiS is different from the underlying bone tissue, and the surface of the FMiS is covered with an osteoid seam (Fig. 2).…”

“…(22,23) Although studies indicate that sclerostin inhibition promotes both remodeling and MBF as evidenced from sclerostin-deficient mice, (24) it is the MBF that has the potential to rebuild trabecular bone structures. In a recent study (25) we enhanced this histological definition by first describing the histological finding of MBF on trabecular bone with no evidence of previous resorption as a "minimodeling structure" (MiS). The MiS was characterized by specific histological criteria: (a) the base of the MiS had a smooth lamellar BS and (b) the lamellar pattern of the MiS differed from that of the base of the BS.…”

Histochemical characteristics on minimodeling-based bone formation induced by anabolic drugs for osteoporotic treatment

“…Therefore, Kobayashi et al (2003) emphasized that minimodeling should be taken into an account when dealing with parameters related to osteoid volume and mineralization, and therefore, supported Frost's hypothesis that minimodeling can continue throughout human life. Sano et al (2018) followed Kobayashi's study to examine bone histomorphometry in 21 bone specimens collected during hip arthroplasty. They proposed that active modeling-based bone formation can be referred to as "forming minimodeling structure".…”