Clinical trial NCT02395315: Alveolar Bone Changes in Diabetes (ABCD) Study
Official title: Placement of Hydrophilic TiZr Implants to Enhance Implant Survival in Diabetic Patients: A Prospective, Two-arm, Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus
Keywords: Diabetes Mellitus
Osseointegration
Bone vascularity
Primary implant stability
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: University of Washington
First posted: 2015-03-23
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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.

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Differences in alveolar bone vascularity among well-controlled and not well-controlled diabetic patients.
timeFrame: Baseline (intra-operative bone sample)
Secondary outcomes:
measure: RANK-L to OPG ratio
timeFrame: Baseline to 8 weeks
Other outcomes:
measure: Differences in alveolar bone mineralization
timeFrame: Baseline (intra-operative bone sample)
measure: ISQ values as a surrogate for implant stability
timeFrame: Time of implant surgery-36 months
measure: Implant survival and success assessment at 3-months, 6-months, 1-year and 3-years post-loading
timeFrame: 3 years
measure: Marginal bone level assessment
timeFrame: 3 years
measure: Implant surgery-related complications
timeFrame: 3 months
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Advanced Education in Periodontology
state: Minnesota
city: Houston
country: United States
facility: University of Texas
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: George Kotsakis, DDS
role: PRINCIPAL_INVESTIGATOR
References: