Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis (AVA)

• Change from Baseline to 3 Months in Mineralizing Surface/Bone Surface (MS/BS) in the Endocortical Compartment, Intracortical Compartment, and Periosteal Compartment of Iliac Crest Bone Biopsies [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Proportion of Bone with Remodeling-Based Formation and Modeling-Based Formation [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Proportion of Overfilled Remodeling Sites [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Change from Baseline to 3 Months in Label Length within each Basic Multicellular Unit (BMU) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Change from Baseline to 3 Months in Mineral Apposition Rate (MAR) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Change from Baseline to 3 Months in Bone Formation Rate (BFR) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Percent of Single or Double Tetracycline Labels per Bone Surface (sLS/BS), (dLS/BS) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Change from Baseline to 3 Months in Intact Parathyroid Hormone (PTH) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Change from Baseline to 3 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Change from Baseline to 3 Months in Serum Osteocalcin [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Change from Baseline to 3 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
• Activation Frequency (Ac.f ) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Adjusted Apposition Rate (Aj.AR) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Number of Samples with Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Percentage of Osteoid Volume (OV)/Bone Volume (BV) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Percentage of Osteoid Surface (OS)/Bone Surface (BS) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Osteoid Thickness (O.Th) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Wall Thickness (W.Th) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
• Percentage of Eroded Surface/Bone Surface (ES/BS) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]

The purpose of this study is to determine how teriparatide or denosumab affects the bone of postmenopausal women with osteoporosis after 3 months of treatment, as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis).

• Drug: Teriparatide
  Administered SC
  Other Names:

  • LY333334
  • Forteo
  • Forsteo
• Drug: Denosumab
  Administered SC
• Drug: Demeclocyline
  Administered orally
• Drug: Tetracycline
  Administered orally
• Drug: Calcium Supplement
  Administered orally
• Drug: Vitamin D
  Administered orally

• Experimental: Teriparatide

  20 micrograms (mcg) teriparatide administered subcutaneously (SC) once every day for 6 months.

  Demeclocycline (DEM): Beginning 18 days prior to Randomization: Days 1, 2, 3 and 16, 17, 18: 150 milligram (mg) DEM will be taken orally every 6 hours; Days 4-15: DEM will not be administered.

  Tetracycline (TET): Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15 and 19 through 22: TET will not be administered.

  Calcium: Approximately 1000 milligrams per day (mg/day) administered orally.

  Vitamin D: Approximately 800 to 1200 International Units per day (IU/day) administered orally.

  Interventions:

  • Drug: Teriparatide
  • Drug: Demeclocyline
  • Drug: Tetracycline
  • Drug: Calcium Supplement
  • Drug: Vitamin D
• Active Comparator: Denosumab

  60 mg denosumab administered SC once in 6 months.

  Demeclocycline (DEM): Beginning 18 days prior to Randomization: Days 1, 2, 3 and 16, 17, 18: 150 milligram (mg) DEM will be taken orally every 6 hours; Days 4-15: DEM will not be administered.

  Tetracycline (TET): Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15 and 19 through 22: TET will not be administered.

  Calcium: Approximately 1000 mg/day administered orally.

  Vitamin D: Approximately 800 to 1200 IU/day administered orally.

  Interventions:

  • Drug: Denosumab
  • Drug: Demeclocyline
  • Drug: Tetracycline
  • Drug: Calcium Supplement
  • Drug: Vitamin D

Inclusion Criteria:

• Ambulatory, postmenopausal women (no vaginal bleeding for at least 2 years prior to screening) with osteoporosis
• Bone mineral density (BMD) T-score of at least -2.5 at femoral neck (FN), total hip (TH), or lumbar spine (LS) (L1-L4, with at least 2 evaluable vertebrae), with or without atraumatic fracture after menopause, OR
• BMD T-score of at least -1.5 at FN, TH, or LS (L1-L4, with at least 2 evaluable vertebrae), and 1 or more atraumatic fractures after menopause (vertebral or nonvertebral). Nonvertebral fracture sites allowed are wrist, hip, pelvis, rib, humerus, clavicle, leg (femur, tibia, and fibula, excluding ankle)
• Laboratory values for serum calcium, parathyroid hormone (PTH), and alkaline phosphatase must be within the normal reference range

Exclusion Criteria:

• Has an increased risk of osteosarcoma (bone tumor); this includes Paget's disease of bone, a previous bone tumor, or radiation involving the skeleton
• Has an allergy or intolerance to teriparatide or denosumab AND/OR is a poor candidate for teriparatide or denosumab treatment (investigator should refer to local product prescribing information)
• Has a history of exposure to demeclocycline (DEM) or tetracycline (TET) therapy in the 12 months prior to screening or a known allergy to DEM or TET
• Has a condition that could put the participant at additional risk of an adverse event due to the bone biopsy procedure (e.g. bleeding disorder)
• Has undergone 2 previous iliac crest bone biopsies (1 in each iliac crest)
• Has a 25-hydroxyvitamin D concentration of <10 nanogram per milliliter (ng/mL)
• Has currently active or suspected (within 1 year prior to enrollment) diseases that affect bone metabolism, other than osteoporosis (such as renal osteodystrophy, hyperthyroidism, osteomalacia, or hyperparathyroidism)
• Has a history of certain cancers within 5 years prior to trial entry
• Current or recent (within 1 year prior to enrollment) celiac disease, inflammatory bowel disease, gastric bypass, or other malabsorption syndrome
• Has significantly impaired hepatic or renal function
• Has had treatment with systemic glucocorticoids in doses ≥5 milligrams/day (mg/day) prednisone/day or equivalent in the 6 calendar months prior to screening
• Has taken any intravenous osteoporosis medication
• Has had prior treatment with other bisphosphonates and not been off of them for a specific period of time before trial entry
• Has participated in any other clinical trial studying teriparatide, PTH, PTH analog, or denosumab, or prior or current treatment with teriparatide, PTH, PTH analog, or denosumab