Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease
Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease
Kidney disease patients have a variety of bone disorders that result in bone loss and
 fractures. The mechanisms of these bone disorders are not clear but may be related to
 abnormal modification of a bone protein known as collagen. Therefore, the investigators are
 conducting this research study to identify underlying mechanisms that are responsible for the
 disruption of bone collagen and determining whether the abnormal bone collagen impairs bone
 strength. The investigators intend to identify these mechanisms through studying
 relationships between kidney disease and bone strength via bone imaging, bone biopsy and
 non-invasive measures from blood and skin.
Kidney disease patients have abnormal protein (bone collagen) modifications in their bone
 that may increase the risk of breaking a bone (fracture). Preventing bone collagen from
 becoming abnormal may decrease the risk of breaking a bone, such as the spine or hip.
 Currently, the effect of abnormal bone collagen on bone strength is not fully defined, and
 there are no methods to measure the abnormal protein content without a bone biopsy. The
 purpose of this study is to define the effects of bone collagen on bone strength and to
 identify non-invasive markers that will tell us how much abnormal collagen is in the bone. If
 the investigators are able to identify a non-invasive marker of abnormal bone protein then
 they may be able to prevent the build-up of this protein and lower the risk of a fracture.

 If the participant chooses to be in the study, the investigators will get information from
 the participant's medical records such as diagnosis, the medicines and treatments prescribed
 by the participant's doctor, and the participant's lab test results.

 There will be two study visits, each lasting about 3 hours.

 Visit 1: At the baseline visit, study procedures include:

 -  Completing medical history, physical activity level, and dietary questionnaires for
 calcium and vitamin D.

 -  Blood sample

 -  Bone Imaging will: dual energy X-ray absorptiometry (DXA) to measure bone mineral
 density, high-resolution peripheral quantitative computed tomography (HRpQCT) to measure
 bone quality, and back x-rays to assess for the presence of spine fractures.Females who
 are able to become pregnant will also provide a urine specimen for pregnancy testing. (A
 negative pregnancy test is required prior to bone imaging.)

 -  Measure levels of Advanced Glycation End products (AGEs) in the skin of the
 participant's forearm and also in the participant's bone by bone biopsy. Advance
 Glycation End products may play a role in the development of weakened bone due to
 chronic kidney disease.

 Visit 2: The participant's second visit will occur within 6-months of enrollment. At this
 visit, the participant will undergo a bone and muscle biopsy at the hip area under conscious
 sedation and a localized pain numbing medicine. The bone biopsy provides detailed information
 about the quality of the participant's bone that cannot be obtained through other tests like
 x-rays or blood tests. The investigators will use the bone biopsy to determine the amount of
 abnormal protein in the participant's bone. The muscle biopsy informs about the health of the
 participant's muscle fibers and allows us to detect any muscle mass wasting associated to
 chronic kidney disease. Since the piece of muscle is taken form the bone biopsy, no extra
 incision is needed.

 The duration of the participant's participation from start of antibiotics through the actual
 bone biopsy will be approximately 3 weeks and 5 days (26 days).
Inclusion Criteria:

 -  Chronic kidney disease stage 3, 4 or 5

 -  Stable dose of vitamin D for 2-months

 Exclusion Criteria:

 -  Dialysis

 -  Current use or treatment in the past one year with oral or inhaled glucocorticoids for
 more than 90 days.

 -  Current use or treatment in the past one year with sex hormone/SERM therapy for more
 than 30 days.

 -  Any use of bisphosphonates.

 -  Use of anti-osteoporosis therapies (denosumab, teriparatide, calcitonin or
 anti-sclerostin antibodies) in last 2 years.

 -  Any solid organ transplant or bone marrow transplant (Not including skin or cornea).

 -  Patients on non-aspirin anticoagulants that cannot be reasonably held for biopsy.

 -  Any cancers within 5-yrs of diagnosis that were metastatic to bone, and that are not
 in complete remission

 -  Any history of leukemia, multiple myeloma, lymphoma, amyloid or paraproteinemias.

 -  Any congenital or acquired collagen of bone diseases other than osteoporosis or renal
 osteodystrophy (Including but not limited to: Osteogenesis Imperfecta, X-Linked
 Hypophosphatemic Rickets, Pagets or Cushings Disease).

 -  History of Primary Hyperparathyroidism within 2-years of Parathyroidectomy.

 -  Hypoparathyroidism - primary or post-surgical

 -  Hyperthyroidism - if untreated and not on stable dose of medication for 6 months

 -  Hypothyroidism - if untreated and not on stable dose of medication for 6 months

 -  Non-ambulatory

 -  Bilateral lower extremity amputations.

 -  Weight >300 lbs.

 -  Medical disease - end stage heart, end stage liver, celiac disease and other
 intestinal malabsorption