Alveolar Bone Changes in Diabetes (ABCD) Study
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Observational

Summary: 
      Type 2 Diabetes Mellitus (DM) is a very prevalent metabolic disorder in the adult population
      affecting roughly 17.7 million people in the US alone. The harmful effect of DM on implant
      integration and survival has been attributed to vascular complications in the alveolar bone
      that lead to compromised blood supply and decreased bone density. Nonetheless, the specific
      detrimental effects of DM in the alveolar bone have not been investigated in humans.

      People with DM generally lose more teeth than persons without diabetes, but implant placement
      in not well controlled diabetics is not routinely performed due to the lack of relevant
      evidence and the risk for implant failure and associated complications. Chemically modified,
      micro-rough, hydrophilic (SLActive®) titanium implant surfaces have been shown to accelerate
      osseointegration of dental implants placed in diabetic animals. It has been hypothesized that
      this enhanced biologic response is due to the biocompatibility and hydrophilicity of the
      surface that actively attracts blood and is populated by progenitor cells, and growth factors
      that improve stromal cell differentiation.

      Hypotheses:

      It is hypothesized that hyperglycemia results in compromised vascularity in the mandible.
      Thus, hydrophilic TiZr implant surfaces (Roxolid®) that actively attract fluids and possess
      excellent osteoconductive properties, may enhance peri-implant bone response in diabetic
      patients to levels comparable to well-controlled diabetics.
    

Detailed description: 
      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%<HbA1c≤10%) seeking implant placement in
      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.
    

Intervention name(s): Well-controlled diabetic (WC); Poorly controlled diabetics (PC)
Intervention type(s): Device; Device
Intervention description(s): Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible.; Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adult patients with diagnosed type II DM exhibiting at least one edentulous site in the
        posterior mandible or canine region presenting with levels of HbA1c >7.5% & <10% for
        enrollment in the PC group and HbA1c ≤ 7.0% for enrollment in the WC group.
      
Keywords: Diabetes Mellitus; Osseointegration; Bone vascularity; Primary implant stability