Knee Osteoarthritis Outcome Measures in Arthritic Patients With Osteoporosis
Knee Osteoarthritis Outcome Measures in Arthritic Patients With Osteoporosis
The purpose of this study is to generate proof of concept human data by evaluating
 osteoarthritis outcome measures in arthritic patients that are prescribed Forteo® as the
 standard of care to treat their primary diagnosis of osteoporosis.
The traditional treatment paradigm for osteoarthritis (OA) involves palliative strategies
 focused on pain management and joint replacement. The longstanding inability to develop
 disease-modifying therapies that can rejuvenate joint cartilage is a great unmet need
 considering that diarthrodial and spinal OA is the most prevalent disease in the US, equal in
 numbers to the next top 4 disorders combined (heart, pulmonary, mental health and diabetic
 conditions) (CDC, 2009). Thus, the development of an effective remittive treatment for OA is
 a vital public health initiative with potential for tremendous impact. Our long-term research
 objective is to test a radically different strategy for treatment of OA that is based on
 findings recently published in Science Translational Medicine (Sampson et al., 2011) that
 identified human parathyroid hormone1-34 (teriparatide) as a chondroregenerative agent in a
 murine model of OA. Suggesting a parallel effect in human OA, data mined from the
 NIH-sponsored OA Initiative revealed improved WOMAC knee function scores in arthritic
 subjects coincidentally prescribed teriparatide (trade name: Forteo®) to treat osteoporosis.
 These preclinical and human data provide compelling rationale to study Forteo® as a novel OA
 therapy directed at improving joint structure and function. The central aim of our overall
 research program is to challenge the paradigm that cartilage loss in OA is irreversible.
 Thus, our long-term programmatic goal is to test Forteo® as the first and only
 disease-modifying treatment for OA with potential to rapidly impact clinical care. To achieve
 this, we have been developing a clinical trial where subjects with medial compartment
 Kellgren Lawrence (K-L) stage II-III knee OA will receive either Forteo® or Prolia® (a brand
 of denosumab) for two years. Disease progression will be assessed via structural, biomarker
 and functional outcomes at various time points out to 24 months post-initiation of therapy.
 Since Forteo® is a widely used therapeutic in patients with osteoporosis (OP)-related severe
 bone loss, we propose to examine OA outcomes in OP patients with concomitant knee OA. This
 pilot study described here that tests the hypothesis that patients with unilateral or
 bilateral knee OA (Kellgren-Lawrence grade II-III) that are prescribed Forteo® to treat their
 primary diagnosis of OP will demonstrate improved physical function (Timed-Up-And-Go),
 improved patient-reported outcomes (PROMIS 12a, v1.0), and increased blood levels in the
 cartilage anabolic marker type II collagen C-propeptide. Completion of this proposed
 experimental design would provide critical proof-of-concept preliminary data supporting the
 use of biomarkers, physical function testing and questionnaire-based functional assessment to
 study OA in patients.
INCLUSION CRITERIA:

 -  Age: 40-80 years (inclusive)

 -  Gender: male or female (non-pregnant)

 -  Fluent in written and spoken English

 -  Patients capable of giving informed consent

 -  Primary diagnosis of osteoporosis that will be treated with either Forteo® to induce
 bone anabolism or Prolia® by the study investigator as part of patient's standard of
 care treatment

 -  Symptomatic, medial compartment knee OA with a Kellgren-Lawrence (K-L) score between
 II-III (documented in the medical record by previously collected knee series
 radiography). Radiographs to be performed within past two years.

 EXCLUSION CRITERIA:

 -  Age < 40 or >80 years

 -  Cognitive impairment

 -  Pregnancy

 -  Non-English speaking persons

 -  History of hyperparathyroidism, hypercalcemia, current/recent renal stones, or
 malignancy

 -  Depression (currently taking home medication)

 -  History of inflammatory disease (colitis, rheumatoid arthritis, psoriasis, lupus,
 scleroderma, spondylitis)

 -  Use of immunosuppressants, chemotherapy, or radiotherapy

 -  BMI, angular deformity and K-L score of the contralateral knee (if the OA is
 bilateral) will be noted as covariates