Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?

Inclusion Criteria: * Generally healthy, community-dwelling ambulatory post-menopausal women. * Able and willing to sign informed consent. * Age 60 to 89. * Have osteoporosis defined as follows: * BMD T-score of the lumbar spine, femur neck, total proximal femur or .3 radius of -2.5 to -4.0; note: the lumbar spine must include two vertebrae that are evaluable by DXA in the opinion of the investigator. OR * BMD T-score of the lumbar spine, femur neck, total proximal femur or .3 radius of -1.5 or lower and either an atraumatic (in the opinion of the investigator) nonvertebral fracture; \[note: nonvertebral fracture sites include the wrist, hip, pelvis, ribs, humerus, clavicle, femur, tibia and fibula\] or a minimum of two mild or one moderate or severe atraumatic vertebral fractures (defined using the Genant visual semi-quantitative scale). * Baseline serum 25(OH)D concentration \> 20 ng/ml and \< 60 ng/ml. * Able and willing to receive daily subcutaneous injections using a Forteo® pen. Exclusion Criteria: * History of exposure to external beam or implant radiation therapy involving the skeleton. * Paget's disease or unexplained elevations of alkaline phosphatase. * Any history of venous thrombosis including deep vein thrombosis, pulmonary embolism, retinal vein thrombosis and superficial phlebitis. * Documented atherosclerotic vascular disease, including but not limited to prior myocardial infarction, angina, atrial fibrillation, stroke and TIA. * Marked hypertriglyceridemia (\>500 mg/dl). * History of prior treatment with estrogen resulting in hypertriglyceridemia (\> 500 mg/dl). * Serum calcium, alkaline phosphatase, PTH or TSH outside the normal reference range. * History of nephrolithiasis or urolithiasis within 10 years prior to enrollment; those with a history of nephro- or urolithiasis must have an appropriate radiology study (e.g., IVP or KUB) within six months documenting absence of stones. * Baseline 24-hour urine calcium \> 250 mg. * Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis. * History of any form of cancer except adequately treated squamous cell or basal cell skin carcinoma. * Use of active vitamin D analogs or high dose vitamin D (≥50,000 IU weekly) in the last year. * Active or suspected diseases (within 1 year prior to enrollment) that affect bone metabolism, e.g., renal osteodystrophy, hyperthyroidism, osteomalacia, hyperparathyroidism. * Known allergy, hypersensitivity, contraindication or intolerance to teriparatide or raloxifene. * History of vaginal bleeding within the past year. * Renal failure or substantial hepatic impairment. Note "renal failure" is defined as a calculated creatinine clearance (using the Cockroft-Gault formula) of ≤ 35 ml/minute. * Severe disease, e.g., cardiac, hepatic, pulmonary, etc., which may limit ability to complete this study. Specifically, significantly impaired hepatic function (ALT or GGT 3x the upper limit of normal. * Known malabsorption syndromes, e.g., celiac disease, active inflammatory bowel disease, gastric bypass, etc. * Use of anion exchange resins (e.g., cholestyramine) in the past month. * Current use of warfarin (coumadin). * Current use of highly protein-bound drugs including diazepam, diazoxide and lidocaine. * Current use of digoxin. * Any prior use of bisphosphonates, denosumab, strontium, fluoride, teriparatide or parathyroid hormone. * Prior use of estrogen, raloxifene, calcitonin or testosterone will be allowed if discontinued more than six months previously. Low dose intra-vaginal estrogens (0.3 mg or less of conjugated equine estrogen or equivalent) may be continued throughout the study. * Treatment with glucocorticoids in doses ≥ 5 mg prednisone daily for \> 30 days in the prior year. * Treatment with other drugs known to affect bone metabolism, e.g., anticonvulsants except benzodiazepines or gabapentin, within the prior year. Note: oral calcium supplementation, vitamin D supplementation or diuretic use that has been stable for six months are allowed). * Treatment within the last 30 days with any drug that has not received regulatory approval. * Metal in spine precluding spine QCT. * Any condition that may interfere with evaluation of at least two lumbar vertebrae determined on VFA performed at time of screening. Examples include confluent aortic calcification, severe osteoarthritis, spinal fusion and lumbar spine fractures.