Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered parathyroid hormone (PTH) tablet on serum markers of bone formation [N-terminal propeptide of Type I procollagen (PINP) and osteocalcin (OC)] and bone resorption [crosslinked C-telopeptide (CTX)], bone mineral density (BMD) and safety in postmenopausal women with low BMD or osteoporosis. In this 6-month, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5mg or placebo daily. Biochemical markers were assessed at 1, 2, 3 and 6months and BMD of lumbar spine, total hip and femoral neck was measured at 6months. Biochemical marker changes were dose dependent with minimal or no effect at the two lowest doses. At the highest dose (2.5mg once daily), serum PINP and OC levels increased 30% within 1month after oral PTH initiation (p < 0.0001), remained elevated through 3months and were back to baseline at 6months. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6months respectively (both p ≤ 0.02). At 6months, 2.5mg tablets increased mean BMD vs placebo of the lumbar spine by 2.7%, total hip by 1.8%, and femoral neck by 2.8% (all p ≤ 0.01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.