Early Effects of Abaloparatide on Tissue-based Indices of Bone Formation and Resorption
Early Effects of Abaloparatide on Tissue-based Indices of Bone Formation and Resorption
Effects of abaloparatide on bone formation and resorption in postmenopausal women with
 osteoporosis.
The objective of this study is to measure the early effects of abaloparatide on tissue-based
 bone formation using samples obtained by iliac crest bone biopsy after quadruple fluorochrome
 labeling.
Inclusion Criteria

 Subject must meet all of the following criteria to be eligible to participate in this
 study:

 1. The subject is a healthy ambulatory postmenopausal female from 50 to 85 years of age
 (inclusive) with osteoporosis.

 2. The subject has been postmenopausal for at least 5 years. Postmenopausal status will
 be established by a history of amenorrhea for at least 5 years and by an elevated
 follicle stimulating hormone (FSH) value of ≥ 30 IU/L.

 3. The subject has a BMD T-score ≤ -2.5 at the lumbar spine (L1-L4) or hip (femoral neck
 or total hip) by DXA or lumbar spine or hip BMD T-score ≤ -2.0 with a history of low
 trauma vertebral, forearm, humerus, sacral, pelvic, hip, femoral, or tibial fracture
 sustained within 5 years prior to enrollment. These fractures must be documented by
 radiograph or hospital report.

 4. The subject is in good general health as determined by medical history and physical
 examination (including vital signs), has a body mass index (BMI) of 18.5 to 33,
 inclusive, and is without evidence of clinically significant abnormality in the
 opinion of the Investigator.

 5. The subject has serum calcium (albumin-corrected), PTH (1-84), phosphorus, and
 alkaline phosphatase levels all within the normal range during the Screening Period.
 Any patient with an elevated alkaline phosphatase value, and who meets all other entry
 criteria, is required to have a normal bone-specific alkaline phosphatase result to be
 enrolled.

 6. The subject has serum 25-hydroxyvitamin D values ≥ 20 ng/mL and within the normal
 range. Patients with serum 25-hydroxyvitamin D levels < 20 ng/ml may be treated with
 vitamin D3 and re-tested once.

 7. The subject's resting 12-lead electrocardiogram (ECG) obtained during screening shows
 no clinically significant abnormality.

 8. The subject has read, understood, and signed the written informed consent form.

 Exclusion Criteria:

 Subjects with any of the following characteristics are not eligible to participate in the
 study:

 1. Presence of abnormalities of the lumbar spine that would prohibit assessment of lumbar
 spine BMD, defined as having at least 2 radiologically evaluable vertebrae within
 L1-L4.

 2. Unevaluable hip BMD or patients who have undergone bilateral hip replacement
 (unilateral hip replacement is acceptable).

 3. History of bone disorders (eg, Paget's disease) other than postmenopausal
 osteoporosis.

 4. Clinically significant abnormality of serum hemoglobin, hematocrit, white blood cells
 (WBC) and platelets, coagulation, or usual serum chemistry: electrolytes, renal
 function, liver function and serum proteins.

 5. Unexplained elevation of serum alkaline phosphatase.

 6. History of radiotherapy (radiation therapy), other than radioiodine.

 7. History of bleeding disorder that would preclude a bone biopsy, in the opinion of the
 Investigator.

 8. History of chronic or recurrent renal, hepatic, pulmonary, allergic, cardiovascular,
 gastrointestinal, endocrine, central nervous system, hematologic or metabolic
 diseases, or immunologic, emotional and/or psychiatric disturbances to a degree that
 would interfere with the interpretation of study data or compromise the safety of the
 patient.

 9. History of Cushing's disease, hyperthyroidism, hypo- or hyperparathyroidism, or
 malabsorptive syndromes within the past year.

 10. History of significantly impaired renal function (serum creatinine > 177 µmol/L or >
 2.0 mg/dL). If the serum creatinine is > 1.5 and ≤ 2.0 mg/dL, the calculated
 creatinine clearance (Cockcroft-Gault) must be ≥ 30 mL/min.

 11. History of any cancer within the past 5 years (other than basal cell or squamous cell
 cancer of the skin).

 12. History of osteosarcoma at any time or a history of hereditary disorders which could
 predispose the patient to osteosarcoma.

 13. History of nephrolithiasis or urolithiasis within the past five years.

 14. Subjects known to be positive for hepatitis B, hepatitis C, human immunodeficiency
 virus infection (HIV-1 or HIV-2). Testing is not required in the absence of clinical
 signs and symptoms suggestive of HIV infection or acute or chronic hepatitis.