PTH(1-34) and Pelvic Fracture Healing - a Randomized Controlled Trial

The incidence rate of pelvic fractures increases dramatically with age, from 5.4 and 3.8 per
10,000 person-years in women and men aged 65 to 69 years to 93.5 and 44.5 per 10,000
person-years in women and men aged 90 years and older, respectively. Pelvic fractures are
accompanied by severe pain, chronic immobility and loss of function and independence in the
elderly. Pelvic fractures consume substantial healthcare resources, and based on
administrative claims data, they are one of the most costly osteoporosis related fractures.
Un-healed fractures, occurring in one-third of pelvic fracture patients at 3 months, can
cause continued pain and impact mobility. With aging of the population, and expected
concomitant increase in the incidence of pelvic fractures, there is a pressing need to find
effective treatments that will accelerate healing. Fracture of the pubic ramus is most
relevant and practical for randomized double-blinded placebo controlled study as this
fracture is accompanied by severe pain and immobility in elderly, is associated with delayed
fracture healing, and is almost always treated non-operatively. The current standard of care
for pelvic fractures includes pain management, patient mobilization, and the prevention of
complications associated with comorbid conditions. The investigators hypothesize that
development of a successful adjunctive therapy to accelerate fracture healing would lead to
improved care and reduce both direct and indirect costs from pelvic fractures. In the
proposed trial the investigators will recruit women and men >65 years of age with acute
osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of treatment
in a placebo controlled double blind study to determine if standard care and teriparatide 20
mcg/day versus placebo for pelvic fractures:

1. Results in earlier evidence of cortical bridging on routine radiographs followed by
confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans
(primary outcome).

2. Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a
reduction in the use of narcotics (secondary outcome).

3. Leads more rapidly to improved functional outcome using a short physical performance
battery to assess lower extremity function (secondary outcome).

The investigators will extend this study with 9 months of open label TPTD to determine if any
potential differences between the placebo and TPTD groups during the 3 months of treatment
are evident and persist over time, even in patients who use TPTD after the three month
placebo controlled intervention. If TPTD can improve fracture healing, this study will have
an impact on the treatment of persons with pelvic fracture who are not surgical candidates
and often face severe pain, chronic immobility, and loss of function in the elderly. A
positive finding of accelerated healing of pelvic fractures would also encourage study of
TPTD for treatment of other osteoporotic fractures.

Inclusion Criteria:

Postmenopausal women and men >65 years of age with acute pelvic fractures, occurring with
minimal trauma, presenting to Helen Hayes Hospital, Hospital for Special Surgery, or New
York Hospital (Cornell Medical). Patients that have either one or multiple pelvic fractures
or sacral and pelvic fractures will be included in the study. Subjects must start treatment
within one month of hip fracture.

Exclusion Criteria:

1. Persons unable to complete the NRS and other surveys based on their mini-mental status
score (≤18; consistent with moderate and severe cognitive impairment)

2. Previously (prior to fracture) non-ambulatory subjects

3. Exclusion criteria related to contraindication or intolerance to TPTD:

1. Hypersensitivity to TPTD

2. Patients with increased risk of osteosarcoma: Paget's disease, history of
radiation exposure

3. Patients with active hypercalcemia

4. Current hyperparathyroidism and other metabolic bone disease including
osteogenesis imperfecta

5. History of multiple renal calculi or renal calculus within the last 2 years

6. Normal alkaline phosphatase levels will not be used as an entrance criterion
because most fracture patients will have elevations due to the acute fracture.
However, the investigators will attempt to obtain lab tests from the period prior
to fracture to determine if they were normal. If unexplained elevations in
alkaline phosphatase are found in labs prior to the fracture we will exclude that
subject.

7. Evidence of metastatic cancer or history of bone cancer or any active cancer
other than basal or squamous cell carcinoma.