Alveolar Bone Changes in Diabetes (ABCD) Study

A high level of evidence exists to support the placement of implants in type 2 diabetics with
glucosylated hemoglobin (HbA1c) levels within the normoglycemic range. Less information is
available for the integration of implants placed in diabetics that cannot achieve good
glycemic control, who may represent up to 50% of the diabetic patient population. Recent data
from the medical literature have unveiled the deleterious effect of uncontrolled diabetes
mellitus (DM) on the bone marrow. The microvascular alterations of DM on skeletal bones lead
to microangiopathy, reduced blood flow and fatty degeneration in the bone marrow. Nascent
theories that are founded upon the observation of increased levels of soluble osteoprotegerin
(OPG) levels in uncontrolled DM implicate disruption of RANKL/OPG signaling as a potential
pathway for the diabetes- related bone alterations. Nonetheless, no data is currently
available on the pathophysiology of the alveolar bone in patients with DM.

It is hypothesized that 1) hyperglycemia results in compromised vascularity in the mandible,
thus 2) hydrophilic TiZr implant surfaces (Roxolid®) that actively attract fluids and possess
excellent osteoconductive properties, may enhance peri-implant bone response in not
well-controlled diabetics (NCD) to levels comparable to well-controlled diabetics (WCD). We
further hypothesize that the expected decreased RANKL/OPG ratio in NCD versus WCD will not
recover during post-surgery bone remodeling. To assess our hypotheses, we will recruit n=21
type II WCD (HbA1c≤7.0%) and n=21 type II NCD (7.5% the mandible. We will collect intra-operative bone specimens at baseline and blood samples to
assess bone structural alterations (H&E stain), microvascular density (immunohistochemistry),
bound RANKL/OPG (immunohistochemistry) and serum RANKL/OPG (ELISA). Implant integration and
success will be assessed at 3, 6, 12 and 36-months.

Obtained results will give dental researchers new insights into the pathophysiology of the
alveolar bone in diabetes and will provide information on the safety and efficacy of implant
placement in type II diabetic patients that cannot control their glycemic status.
Collectively, this work will pave the way for identifying efficacious implant treatment
modalities for persons that live with type II diabetes to alleviate the morbidity associated
with tooth loss in this susceptible population group.

Inclusion Criteria:

Adult patients aged 18-85 years with diagnosed DM2.

History of DM2 for at least two years prior to enrollment.

At least one edentulous site in the canine or posterior mandible regions.

HbA1c >7.5% & <10% for enrollment in the test group.

HbA1c ≤ 7.0% for enrollment in the control group.

Available for follow up at 12 months.

Exclusion Criteria:

Mandibular incisor sites that will not allow bone core retrieval due to limited alveolar
bone width (ridge width <5mm, height <10mm) as confirmed by pre-operative CBCT.

Smokers: current, or ex-smokers with <2 years cessation.

Active periodontal disease.

Medications that affect bone healing (e.g. bisphosphonates or chronic steroids).

Patients who are carriers of transmissible disease(s) that may unnecessarily expose
laboratory personnel to risks.

Participants with a physician-diagnosed osteoporosis (Z-score ≤ -2).

Females during pregnancy or lactation and females that plan to become pregnant in the
following year.

Patients that will not agree to participate in this study or sign the consent form.