Impact of Parathyroid Hormone (PTH) on Osseous Cavity
Condition: Bone Loss; Periodontitis
MeSH terms: Periodontitis
Study type: Interventional
Phase: Phase 1

Summary: 
      Parathyroid hormone (PTH) has potent bone-building actions and has been approved for the
      treatment of osteoporosis as FORTEO by Eli Lilly & Co. Numerous studies have verified its
      effectiveness in increasing bone mass and potential for PTH to positively impact oral bone.
      The hypothesis of this study is that patients administered FORTEO along with periodontal
      (gum) surgery will respond more favorably than patients who receive placebo.

      There will be 40 subjects enrolled in this study. All subjects will receive surgical
      treatment. 20 subjects will receive FORTEO and 20 will receive placebo. Subjects will be
      assigned to study group randomly. Neither the subjects nor the clinicians will know whether
      the subject is receiving FORTEO or placebo.

      Patients will undergo routine periodontal treatment procedures including periodontal surgery.
      Starting from 3 days prior to surgery, all subjects will self-administer FORTEO or placebo
      for 6 weeks. Subjects will be trained for self-administration, a procedure similar to
      diabetic injections. Patients will also take Vitamin D and Calcium by mouth during this time.
      Study outcomes will be measured by blood collection; oral fluid sampling; oral x-ray and
      spine and hip bone density scan; routine periodontal examinations; and an oral health quality
      of life questionnaire.

      Patients of both genders and all ethnicities from age 30-75 years will be included in the
      study. All ethnicities are eligible for entry into study. No vulnerable populations will be
      included. Pregnant/breast-feeding women and women of childbearing potential on no
      contraception will be excluded from the study. Research records will not be linkable to the
      research subjects. Subjects will be randomly assigned to treatment arms and identified by
      initials and numbers. Informed consent forms will be used to obtain consent for participation
      in the study from all subjects prior to enrollment. The Principal Investigator or
      Co-Investigator will explain the details of study involvement and give subjects ample
      opportunity to ask questions.

      It is anticipated that patients on FORTEO will have greater regeneration with periodontal
      therapy as compared to control patients.
    

Detailed description: 
      Parathyroid hormone is an endogenous hormone with potent anabolic and catabolic actions in
      bone. It has recently been approved for the treatment of osteoporosis and is marketed as
      FORTEO by Eli Lilly and Company. Numerous studies in humans have validated its use to
      increase bone mineral density and prevent fractures. Interest has also surfaced in its
      potential application in the treatment of non-osteoporotic fractures and several animal
      studies have supported this local application. Little is known regarding its use in treating
      conditions of the oral cavity, but animal studies suggest that bones of the oral cavity are
      responsive to the anabolic actions of PTH. Furthermore, a recent study indicated that in a
      canine model, PTH was effective at reversing periodontal bone loss. Studies from our
      laboratory indicate that patients with hyperparathyroidism (HPT) do not have an increase in
      periodontal disease as measured by attachment levels. In fact, in our patient population
      there was an increase in osseous activity in patients with HPT in the form of tori and
      exostoses (bony protuberances in the oral cavity). This suggests that increased circulating
      levels of PTH do not adversely impact the oral cavity. Furthermore, in a wound healing animal
      model of bone regeneration, we found that regenerating intramembranous bone was more
      responsive to anabolic actions of PTH than endogenous bone of the vertebrae. These studies
      highlight the potential for PTH to positively impact osseous healing in the oral cavity in
      response to periodontal therapy.

      The study will be double blinded, and patients will be randomized into one of two treatment
      groups (FORTEO or placebo once/daily). Patients will self-administer drug on a QD schedule,
      and take Vitamin D and Calcium, PO, QD, for six weeks. Drug administration will begin three
      days prior to periodontal surgery. Subjects will be followed at post-op, week 3, week 6,
      month 3, month 6, month 9, and month 12 visits. Clinical effects will be measured by serum
      collection, gingival crevicular fluid (GCF) sampling, standard dental radiographs, oral exam
      including perio probing, oral health quality of life questionnaire, and DEXA scans.
    

Intervention name(s): Periodontal surgery; FORTEO; Placebo; Vitamin D and Calcium
Intervention type(s): Procedure; Drug; Drug; Dietary Supplement
Intervention description(s): parathyroid hormone; self-administration for 6 weeks; placebo; self administration for 6 weeks; PO, QD, for six weeks
Intervention MeSH terms: Vitamin D; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: periodontitis; bone regeneration; Parathyroid Hormone; moderate to advanced periodontitis