Ibandronate Treatment Before and After Implant Insertion Impairs Osseointegration in Aged Rats with Ovariectomy Induced Osteoporosis

Abstract

Excessive decreases in bone volume (BV) and bone mineral density (BMD) can lead to osteoporosis, potentially hindering implant osseointegration. Bisphosphonates are commonly used to combat osteoporosis by slowing osteoclast‐mediated resorption; however, functional osteoclasts are integral to bone remodeling and, thus, implant osseointegration, potentially contraindicating bisphosphonate use during implantation. To optimize the use of implant technologies in patients with compromised bone structure and metabolism, we need a more complete understanding of the biological response to surface design. The goal of this study was to assess the effects of osteoporosis and bisphosphonates on osseointegration of titanium (Ti) implants with microstructured surfaces, which have been shown to support osteoblast differentiation in vitro and rapid osseointegration in vivo . Forty, 8‐month‐old, virgin, female CD Sprague Dawley rats underwent ovariectomy (OVX) or sham (SHOVX) surgery. After 5 weeks, animals were injected subcutaneously with either the bisphosphonate (BIS), Ibandronate (25 µg/kg), or phosphate‐buffered saline (PBS) every 25 days. 1 week after the initial injection, Ø2.5mm × 3.5mm microrough (SLA; grit‐blasted/acid etched) implants were placed transcortically in the distal metaphysis of each femur resulting in four groups: 1) SHOVX+PBS; 2) SHOVX+BIS; 3) OVX+PBS; and 4) OVX+BIS. After 28d, qualitative properties of the bone and implant osseointegration were assessed using micro‐computed tomography (microCT), calcified histomorphometry (Van Gieson's stain), and removal torque testing. microCT revealed decreased bone volume in OVX rats, which was slowed by bisphosphonate treatment. Reduced bone‐to‐implant contact (BIC) was evident in OVX+PBS compared to SHOVX+PBS. Although BV/TV was increased in OVX+BIS compared to OVX+PBS, bisphosphonate treatment had no effect on BIC. Removal torque testing revealed a higher maximum torque, torsional stiffness, and torsional energy in SHOVX compared to OVX with no effects due to bisphosphonate treatment. Our results show that osseointegration is decreased in osteoporotic animals. Ibandronate halts the progression of osteoporosis but does not enhance osseointegration. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

Titanium implant surface properties enhance osseointegration in ovariectomy induced osteoporotic rats without pharmacologic intervention

“…Additionally, the XPS results revealed a surface composition similar to what was reported on hydrophilic surfaces compared to hydrophobic surfaces (Lotz et al, ). These results also support our findings reported for the SLA implant confirming batch‐to‐batch fabrication consistency (Lotz et al, ). Although the processing technique used in this study allowed accurate separation between the effects of the nanostructures and the surface hydrophilicity, the altered surface chemistry associated with the reduced carbon contamination could directly contribute to the positive effects observed around hydrophilic implants.…”

“…Additionally, the XPS results revealed a surface composition similar to what was reported on hydrophilic surfaces compared to hydrophobic surfaces (Lotz et al, 2016). These results also support our findings reported for the SLA implant confirming batch-to-batch fabrication consistency (Lotz et al, 2019). Although the processing technique translates into enhanced contact and distal osteogenesis in vivo (Salvi et al, 2015).…”

“…All animals had access to water ad libitum for the duration of the study; however, OVX animals were pair fed a phytoestrogen‐free diet (Advanced Protocol Verified Casein Diet 10 IF, LabDiet, St. Louis, MO, USA) to age‐matched sham OVX controls. The success of the pair feeding regimen was verified by weekly weighing of all animals for the duration of the study, as described previously (Lotz et al, ).…”

“…Local regulatory factor production has also been shown to be sensitive to microstructured Ti implants. In addition to the high production of negative regulators of osteoclast activity, cells produce high levels of osteocalcin and osteopontin (Boyan, Olivares-Navarrete, Berger, Hyzy, & Schwartz, 2018;Lotz et al, 2019). Osteocalcin promotes the chemotaxis, adhesion, and spreading of osteoclasts (Glowacki, Rey, Glimcher, Cox, & Lian, 1991;Ritter, Farach-Carson, Butler, Farach-Carson, & Butler, 2009), while osteopontin plays a role in anchoring osteoclasts to the mineralized bone matrix (Reinholt, Hultenby, Oldberg, & Heinegard, 1990).…”

“…Much of the research in the field of implantology has been limited to healthy animals and patients. A recent study demonstrated primary osteoblasts isolated from osteoporotic rats produced greater amounts of pro‐osteogenic factors compared to osteoblasts isolated from healthy rats when cultured on hydrophobic and microrough Ti surfaces in vitro (Lotz et al, ). This suggests that the successful outcomes of implanted materials in osteoporotic patients may not need to rely on pharmacologic intervention.…”