The purpose of this study is to evaluate teriparatide (TP) as a chondroregenerative therapy for human knee osteoarthritis (OA). The central hypothesis to be tested is that TP supports structural modification of the joint and improves biomarker, functional and patient-reported measures of knee OA.

This is a prospective, randomized, placebo controlled, double blinded, crossover study. The investigators will identify, recruit and enroll 80 subjects with symptomatic, unilateral medial compartment knee OA. Enrolled subjects will be randomized into equal TP (in the FDA approved form, Forteo) or placebo arms of 40 subjects each (includes allowance for a 25% dropout rate with no replacements). All subjects will be treated for 24 weeks, then followed for an additional 24 weeks to assess the durability of any observed effects. The trial incorporates a crossover design, based on interim analysis of the 24 week outcome data after every subject has completed the 24 week treatment period. If positive effects on structural and/or biomarker measures are apparent from the interim analysis, placebo treated subjects will be offered TP (in the FDA approved form, Forteo) and followed for an additional 24 weeks. If the placebo subjects who choose to participate in the crossover treatment have not yet completed the 48 week visit, it will not occur. These subjects will begin the crossover portion 24 week treatment and monitoring period when they receive the TP pens (in the FDA approved form, Forteo).

Inclusion Criteria:

1. male or female 40 to 60 years old.
2. radiographic evidence of Kellgren-Lawrence score (K-L score) grade I-II OA in the affected knee
3. unilateral symptomatic knee OA
4. willingness to forgo potential standard of care treatments (hyaluronic acid and cortisol injections) for knee pain for the duration of the study
5. body Mass Index of ≤40
6. normal screening vitamin D levels (≥20 and ≤100 mg/ml)
7. normal screening serum calcium level (8.5- 10.2 mg/dL)
8. a negative screening serum pregnancy test for premenopausal women

Exclusion Criteria:

1. history of primary hyperparathyroidism disease, hypercalcemia, or persistently abnormal intake PTH levels (≥10 or ≤65 pg/ml)
2. history of musculoskeletal malignancy or solid organ carcinoma
3. active renal disease defined by a creatinine clearance of <35 or history of kidney stones within the past year
4. use of anticonvulsant or digoxin therapy
5. inflammatory disease (bowel disease, spondylitis, lupus, fibromyalgia, psoriasis, rheumatoid arthritis, etc)
6. current or past treatment with teriparatide
7. use of immunosuppressants
8. severe claustrophobia, retained eye or skull metal fragments, metal hardware in or around the affected knee or other standard contraindications to MRI (cochlear implants, pacemakers)
9. dementia, cognitive impairment or other factors that referring provider feels would prevent ability to obtain informed consent and/or follow study protocol
10. pregnancy or intent to become pregnant in the two and a half years following enrollment
11. women who are currently breastfeeding
12. Paget's disease
13. osteoporosis diagnosis by DXA in medical history (T-score less than or equal to -2.5)
14. reliance on assistive walking devices (canes, walkers, braces, etc.)
15. participation in concurrent clinical studies involving investigational medications

Researchers, providers, and subjects will be blinded to treatment group so that outcomes will not be influenced by expectations about the experimental treatment.