Pilot Study to Evaluate Knee Osteoarthritis Outcome Measures in Arthritic Patients Prescribed Forteo or Prolia for Osteoporosis

Brief Summary

Detailed Description

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.

Primary Outcomes

Secondary Outcomes

• Patient reported outcomes(2 years)
• Physical function(2 years)
• Urine levels(2 years)