Effects of ovariectomy on bone turnover, porosity, and biomechanical properties in ovine compact bone 12 months postsurgery

Abstract

Compact bone makes up approximately 80% of the human skeleton by mass; but there are little data available on the effects of increased bone turnover on compact bone mechanical and material properties. This study addresses this question by measuring intracortical remodeling, resorption cavity number, and porosity in an ovariectomized (OVX) sheep model, and measures changes in biomechanical properties. Thirty-eight sheep were divided into two groups. Group 1 were controls (n ¼ 19), and Group 2 were ovariectomized (OVX; n ¼ 19). Fluorochrome dyes were administered intravenously to both groups at five time points over 12 months post-OVX to label sites of bone turnover. At 12 months post-OVX all animals were euthanized. Samples were harvested from the left metatarsal and were analyzed for intracortical bone turnover at five time points, the number of resorption cavities, and the level of intracortical porosity. The effects of these parameters on bone biomechanical properties were then measured. Bone turnover was increased in the OVX group at 6, 9, and 12 months (p < 0.05). Resorption was also higher in the OVX group at 12 months (p < 0.05). Furthermore, porosity was significantly increased in the OVX group at 12 months (p < 0.05). Stiffness and yield strength were reduced in the OVX group compared to controls (p ¼ 0.05). Ultimate compressive strength and work to fracture did not differ between groups. These findings provide new insights into the mechanisms and effects of increased bone turnover on bone material and microstructural properties. Keywords: bone turnover; porosity; ovariectomy; ovine animal model Bone turnover is an important determinant of the structural integrity of bone. It is a crucial process of tissue renewal that normally occurs at an optimal physiological rate for maximum bone strength in a healthy individual. 1 Any change to the optimal bone turnover rate, such as the increase that occurs following ovariectomy (OVX) or menopause, has the potential to dramatically change the bone at microstructural and material levels. High bone turnover can have the effect of increasing remodeling spaces, accelerating bone loss, increasing stress concentrations, and increasing cortical porosity, each of which can undermine bone mechanical properties. A precise definition of bone quality remains elusive, however; bone turnover and microarchitecture are considered to be two important contributors to this phenomenon along with mineralization, microdamage, and collagen content. Thus, these parameters are important considerations in the pathophysiology of skeletal diseases such as osteoporosis and the mechanisms that underlie fracture. 2 Previous studies have shown that bone turnover has a direct influence on fracture risk. 3 It is thought that compact bone is affected by accelerated turnover in two ways. First, more mineralized bone is removed and replaced with younger, less mineralized bone, which reduces the material's local stiffness. Second, the presence of more resorption cavities creates stress concen...

Temporal Changes in Bone Composition, Architecture, and Strength Following Estrogen Deficiency in Osteoporosis

“…However, another study has showed that changes do not occur ubiquitously throughout the proximal femur [8]. In the current study the twelve month estrogen deficient group also showed reduced crystallinity indicative of the increased turnover, which is confirmed by the gene expression data presented and previous 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 F o r P e e r R e v i e w 16 work on these animals [39]. In addition Figure 7 provides epifluorescence histological micrographs confirming the increased turnover in the ovariectomised group relative to the controls.…”

“…High levels of bone turnover are visible after 12 months in (a) OVX bone while low levels are seen in (b) control bone. Histological data on these animals can be found in previous studies from our group [39,40]. 198x99mm (47 x 40 DPI) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 …”

Mechanisms of osteocyte stimulation in osteoporosis

“…These ovine studies also found that, as the animals progressed into long-term oestrogen deficiency, there was no significant difference in cortical compressive strength by 31 months post-OVX (Healy et al 2010;Kennedy et al 2009). …”

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model

“…Ct.Th, Ct.Cs.Th, Ct.Ar, MMI(p), Ecc, BMD, BV, BV/TV, BS, BS/TV, Tb.Th, Tb.N, E.Con, E.Con.D and DA were severely decreased, while Ct.Pe.Pm, Ct.En.Pm, Ct.Po, TV, BS/BV, Tb.Sp, Tb.Pf and SMI were significantly increased in the OVX group compared to the sham group. These alterations provide evidence for increased osteoclastic activity due to estrogen deficiency [73] . It is known that estrogen can inhibit bone resorption and destruction by controlling the number and the activity of osteoclasts [74] .…”