A Phase II Study Evaluating SB-751689 in Post-Menopausal Women With Osteoporosis.

Inclusion:

- Informed consent: Subject is willing and able to provide written informed consent.

- Menopausal status: Ambulatory female aged < 80 years at screening and >5 years
postmenopausal.

- T-Score: A subject with either no or only one prevalent vertebral fracture is eligible
for inclusion if she satisfies one of the following T-score requirements:

If no prevalent vertebral fracture subject must have an absolute BMD value consistent with
a T-score of less than or equal to -2.5 and greater than -4.0 at either the femoral neck,
total hip, trochanter, or lumbar spine, or If one prevalent vertebral fracture subject must
have an absolute BMD value consistent with a T-score of less than or equal to -2.0 and
greater than -4.0 at either the femoral neck, total hip, trochanter, or lumbar spine.

- Suitable vertebra: Two or more vertebra in the range of L1 to L4 that are suitable for
BMD measurement by DXA.

- Protocol compliance: Subject who, in the opinion of the investigator, is willing and
able to comply with the requirements of the protocol.

Exclusion:

- T-Score: Has an absolute BMD value consistent with a T-score less than or equal to
-4.0 at either the femoral neck, total hip, trochanter, or lumbar spine.

- Vertebral fractures: Has >1 prevalent vertebral fracture at the screening visit.

- Non-vertebral fractures: Any previous non-vertebral osteoporosis related/fragility
fracture after age 40.

- Spine deformity: Significant spine deformity which would preclude DXA/QCT assessments.

- BMI: BMI ≥33kg/m2.

- Bone metabolic diseases: Other than osteoporosis, history or concurrent diseases
affecting bone metabolism (e.g., osteomalacia, hyperparathyroidism, hyperthyroidism).

- GI disease: History of major upper gastrointestinal disease

- Malabsorption: Active or history of malabsorption (e.g., history of celiac disease,
irritable bowel syndrome or inflammatory bowel disease).

- Liver disease: Past or current history of liver disease or known hepatic or biliary
abnormalities, (with the exception of previously documented diagnosis of Gilbert's
syndrome).

- Rheumatoid arthritis: Active disease or history of rheumatoid arthritis.

- Nephrolithiasis: History of or active nephrolithiasis (kidney stones).

- Osteosarcoma risk: Subjects at increased risk of osteosarcoma such as those with
Paget's disease of bone or any prior external beam or implant radiation therapy
involving the skeleton.

- Malignancy: Malignant disease diagnosed within the previous 5 years (except resected
basal cell cancer).

- Biological abnormalities: Any clinically relevant biological abnormality found and/or
volunteered at screening (other than those related to the disease under investigation)
which, in the opinion of the investigator, is clinically significant and would
preclude safe participation in this study.

- Surgical and medical conditions: Presence of the following conditions within six
months prior to screening: myocardial infarction, coronary bypass surgery, coronary
artery angioplasty, unstable angina, cardiac arrhythmia, clinically evident congestive
heart failure, or cerebrovascular accident.

- Glomerular filtration rate: Glomerular filtration rate (GFR) <35 mL/min as calculated
by the Modification of Diet in Renal Disease (MDRD) equation as follows: GFR
(mL/min/1.73 m2) = 186 x (Serum creatinine mg/dL)-1.154 x (Age)-0.203 x (0.742 if
female) x (1.210 if African American) (conventional units).

- QT/QTc prolongation: A marked baseline prolongation of QT/QTc interval (e.g., QTc
interval ≥450 msec on the Screening ECG).

- Torsades de Pointes: A history of risk factors for Torsades de Pointes (e.g., heart
failure, hypokalemia, family history of Long QT Syndrome).

- Liver chemistries: Liver chemistries [aspartate aminotransferase (AST), alanine
aminotransferase (ALT) or total bilirubin] exceeding 2-fold the upper limit of the
laboratory-specified reference range, at screening.

- Abnormal serum calcium: Serum calcium (total or albumin-adjusted) outside the central
laboratory reference range at the screening visit.

- Abnormal PTH: PTH (intact or whole) outside the normal range.

- Abnormal creatine phosphokinase: Creatine phosphokinase (CPK) outside the normal
range.

- Abnormal alkaline phosphatase: Alkaline phosphatase outside of the normal range.

- Thyroid hormone replacement: Subjects receiving thyroid hormone replacement therapy
must have a TSH level checked. Subjects will be excluded if TSH levels are <0.1 or
>10.0mIU/L. However, subjects will not be excluded if TSH is in the range 0.1-4.5
mIU/L. If TSH is >4.5 and ≤10.0mIU/mL, measure T4 and exclude the subject only if the
T4 is outside the normal range.

- Vitamin D deficiency: Vitamin D deficiency (serum 25-hydroxy vitamin D < 20ng/mL,
equivalent to 50nmol/L) at screening. Subjects can undergo vitamin D repletion as per
local practice and be re-screened once only for vitamin D levels within the 6-week
screening period. They will remain excluded if the re-screened value is < 20ng/mL.

- Previous strontium or IV bisphosphonate: Any previous treatment with strontium
ranelate or intravenous bisphosphonate.

- Oral bisphosphonates: Any previous treatment with an oral bisphosphonate as follows:

any treatment within the last six months

- one month cumulative treatment within the last 12 months

- three months cumulative treatment within the past two years, or

- two years cumulative treatment within the past five years.

- Fluoride: Treatment with fluoride (dose greater than 10mg/day) within the
previous 5 years for osteoporosis.

- Digoxin: Current therapy with digoxin.

- Bone metabolism drugs: Treatment with other drugs affecting bone metabolism
within the last six months prior to screening:

Chronic systemic corticosteroid [e.g., glucocorticoid, mineralocorticoid] treatment of no
more than 2 intra-articular injections within the past year or use of oral, parenteral, or
long-term, high-dose inhaled corticosteroids. Treatment with any topical corticosteroid
will not exclude the subject from participating.

Hormones [e.g., estrogens/"natural estrogen preparations"(except for nonsystemic vaginal
treatment), 19-norprogestins, SERMs such as raloxifene, anabolic steroids/androgens such as
dehydroepiandrosterone (DHEA) or its sulfated form (DHEAS), nandrolone, tibolone, active
vitamin D analogs/metabolites such as 1,25-dihydroxy vitamin D (calcitriol) or
1alpha-hydroxyvitamin D3 (1-alpha hydroxycholecalciferol), calcitonin].

Calcineurin inhibitors [e.g., cyclosporine, tacrolimus] or methotrexate.

- Previous anabolic agents: Treatment with PTH, PTH analogues or similar anabolic agent
for osteoporosis within the last two years.

- Contraindications: Contraindications to therapy with calcium or vitamin D.

- Pregnancy: Women who are pregnant are not allowed in this study.

- Interfering medications: Vitamin A in excess of 10,000 IU per day, heparin, or
lithium, or anticonvulsant medications except benzodiazepines.

- Investigational drug exposure: Administration of any investigational drug within 90
days preceding the first dose of the study drug.

- Substance abuse: History or current evidence of drug or alcohol abuse within the
previous 12 months.

- Problems swallowing: Inability to swallow a tablet whole.

The following exclusion criteria do not apply to subjects allocated to the open-label
teriparatide group:

- Calcium channel blockers: Current therapy with calcium channel blockers diltiazem and
verapamil.

- Oral Azole Antifungals: Current therapy with any oral azole antifungal.

- Immunosuppressants: Current therapy with cyclosporine or oral tacrolimus.

- Ritonavir: Current therapy with ritonavir.

- Quinidine: Current therapy with quinidine.

- Macrolide Antibiotics: Subjects anticipated to require chronic use of macrolide
antibiotics.

- Alendronate Contraindications: Contraindications to therapy with alendronate.
Additional Exclusion Criteria for Subjects Recruited at QCT Sites

- Hip surgery: History of hip surgery resulting in a metal implant on either the left or
right side that would cause an artefact on a QCT scan.

Additional Exclusion Criteria for Teriparatide Subjects

- Teriparatide contraindications: Contraindications to therapy with teriparatide
according to locally approved datasheet.