Use of Forteo (Teriparatide) in Posterolateral Lumbar Spine Fusion

For patients undergoing spine fusion surgery, non-fusion (or pseudarthrosis) is one of the
major complications that can lead to poor clinical outcomes. Therefore, treatments that
promote or augment fusion are highly desirable. Teriparatide (Forteo, recombinant human
parathyroid hormone [1-34]) is a systemically administered peptide hormone that is
FDA-approved for the treatment of osteoporosis in postmenopausal women or other populations
at high risk for fracture. While teriparatide has been shown to enhance spinal fusion in
several rodent and rabbit studies, no clinical studies to date have examined its effect on
spinal fusion in humans.

This single-site two-year prospective randomized double-blind placebo-controlled study is
designed to examine the effects of peri-operative teriparatide treatment in older adults
undergoing multi-level posterolateral lumbar spine fusion. All eligible patients seen at the
UCSF Spine Center will be invited to enroll in the study. Upon enrollment, patients will have
screening labs drawn in conjunction with their routine pre-operative work-up, to include
complete blood count (CBC), chemistry panel including calcium level, liver function tests
(LFTs) including alkaline phosphatase, parathyroid hormone (PTH) level, and 25-hydroxyvitamin
D level. If eligible after screening labs are completed, they will be scheduled for bone
density (DEXA) scan and be randomized in a 2:1 ratio to receive daily subcutaneous injections
of teriparatide 20 ug/d or placebo. The total duration of treatment will be 12 weeks, with
two weeks pre-operative and 10 weeks post-operative treatment.

Patients will be scheduled to attend all standard post-operative follow-up clinic visits,
which will be at 6 weeks, 3 months, 6 months, and 12 months after surgery. At 3 months post
operative visit, patients will have lab drawn for calcium. At each follow-up visit, AP and
lateral x-ray radiographs will be taken of the lumber spine to assess progression of bone
healing and positioning of any hardware placed. Participants will be asked to complete a pain
Visual Analog Score (VAS), European Quality of Life-5 Dimensions (EQ-5D), and Oswestry
Disability Index (ODI) questionnaire at each visit for assessment of clinical outcomes.
Thin-section helical CT scans of the lumbar spine will be taken at 12 months after surgery
for definitive assessment of fusion. All radiographs will be evaluated by a blinded panel of
three reviewers including a radiologist and a spine surgeon to assess primary outcome.

Inclusion Criteria:

- Patients aged 60-90 years with lumbar spondylosis, spondylolithesis, or adult
degenerative scoliosis, including disc pathology, stenosis, deformity, instability, or
postdecompression revision, who are scheduled to undergo three-level or greater
posterolateral lumbar spinal fusion.

- Willing and able to use a pen-type delivery system to administer daily subcutaneous
injections.

Exclusion Criteria:

- Use of bone morphogenic protein (BMP) posterolaterally during the fusion procedure.

- Previous spinal fusion at the intended fusion levels.

- Prior use of Forteo (teriparatide).

- Use of digoxin.

- Paget's Disease of bone.

- History of primary skeletal malignancy, presence of bone metastases, or previous
skeletal exposure to therapeutic irradiation.

- Elevated serum calcium, serum PTH >70 pg/ml, 25-hydroxyvitamin D <12 ng/mL, or active
liver disease.

- History of symptomatic nephro- or urolithiasis in the past two years.

- History of malignant neoplasm in the past five years, except for superficial basal
cell carcinoma or squamous cell carcinoma.

- Carcinoma in situ of the uterine cervix treated in the past year.