• Change in hardness [ Time Frame: 9 months ]
  Change in hardness will be measured by Ramen nano-indentation and mineralization measured by histomorphometry obtained primary dynamic and secondary structural bone quality outcome values from the pre-treatment baseline to the 6-month endpoint after the 3-month titration period.
• Bone mineral density (BMD) of the femoral neck by dual-energy x-ray absorptiometry (DXA) [ Time Frame: 9 months ]
  To test if 9-months of treatment with etelcalcetide improves femoral neck areal BMD.
• Propensity as measured by T50 [ Time Frame: 9 months ]
  The propensity to calcify soft tissues will be measured by T50 for 9 months of treatment. T50 is a novel serum-based marker that assesses the propensity of calcification in serum. Shorter T50 indicates greater propensity to calcify.

• Bone mineral density (BMD) of the spine by DXA [ Time Frame: 9 months ]
  To test if 9-months of treatment with etelcalcetide improves spine BMD.
• Bone mineral density (BMD) of total hip by DXA [ Time Frame: 6 months ]
  To test if 9-months of treatment with etelcalcetide improves total hip BMD.
• Bone formation rate [ Time Frame: 9 months ]
  Following CT scans, specimens will be embedded in methyl methacrylate and sections will be cut with a rotary microtome and either left unstained or stained with McNeal tetracrome or tartrate resistant acid phosphatase for analysis.
• Mineralization density [ Time Frame: 9 months ]
  An integrated Raman/Nanoindentation system will be used, which permits precise measurement of localized bone tissue properties.

• Chronic Kidney Disease Mineral and Bone Disorder
• Renal Osteodystrophy
• Vascular Calcification
• Hyperparathyroidism; Secondary, Renal

Inclusion Criteria:

For All Aims:

1. Patient has provided informed consent.
2. Patient is 18 years of age or older.
3. Patient must be receiving maintenance hemodialysis for at least 3 months, with adequate hemodialysis with a delivered Kt/V 1.2 or urea reduction ratio (URR) 65% within 4 weeks prior to screening laboratory assessments.
4. Dialysate calcium concentration must be stable for at least 4 weeks prior to screening laboratory assessments.
5. Patient must have severe HPT as defined by two laboratory screening pre-dialysis serum PTH values >9-times ULN for the PTH assay, measured on two consecutive monthly lab checks prior to entering the study.

6. The patient has an uncontrolled PTH defined by KDIGO as a PTH greater than 9 times the upper limit of normal of the assay (720 pg/mL for Rogosin):

   AND one of the following:

   • The patient has never been on cinacalcet OR,
   • The patient received daily cinacalcet for less than 3 months and has been off cinacalcet for at least 3 months prior to enrollment OR ,
   • The patient received daily cinacalcet for more than 3 months and has been off cinacalcet for at least 6 months prior to enrollment OR,
   • The patient received a modified dose of three times weekly cinacalcet and has been off cinacalcet for at least one month prior to enrollment.
7. Scheduled to receive etelcalcetide for the treatment of HPT per standard of care.
8. If receiving vitamin D sterols, patient must have had no more than a maximum dose change of 50% within the 4 weeks prior to screening laboratory assessments, remain stable through randomization, and be expected to maintain stable doses for the duration of the study, except for adjustments allowed per protocol*.
9. Patient must have one screening pre-dialysis serum Ca laboratory value at least at the lower limit of normal for the assay measured within 4 weeks prior to entering the study.
10. A patient receiving calcium supplements must have had no more than a maximum dose change of 50% within 2 weeks prior to screening laboratory assessments and remain stable throughout the study, except for adjustments allowed per protocol*.
11. A patient receiving phosphate binders must have had no more than a maximum dose change of 50% within the 2 weeks prior to screening laboratory assessments, remain stable through, and be expected to maintain stable dose for the duration of the study, except for adjustments allowed per protocol*.
12. The treating physician considers the etelcalcetide dose and timing points described in this protocol as acceptable/optimal for their patient.
13. Female patients must be willing to use highly effective contraception during the study and for 3 months after the last dose of etelcalcetide (unless postmenopausal or surgically sterilized).

For Aim 1:

1. Total alkaline phosphatase ≥ the upper tertile of the reference range for the assay

Exclusion Criteria:

For All Aims:

1. Currently receiving treatment in an investigational device or drug study, or less than 30 days since ending treatment on an investigational device or drug study(s).
2. Currently receiving investigational procedures while participating in this study.
3. Patient with controlled PTH as defined by KDIGO as a PTH of 2 to 9 times the upper limit of normal of the assay.
4. Patients has received a bisphosphonate, denosumab or teriparatide during the 12 months prior to screening.
5. Anticipated or scheduled parathyroidectomy during the study period.
6. Patient has received a parathyroidectomy within 6 months prior to dosing.
7. Scheduled kidney transplant during the study period or anticipated living donor evaluation within three months of recruitment
8. Patient has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator.
9. Bilateral lower extremity amputations or non-ambulatory
10. Metabolic bone diseases not related to the kidney (i.e., Pagets, Osteogenesis Imprefecta)
11. Untreated hyperthyroidism or hypoparathyroidism
12. Malignancy within the last 5 years (except non-melanoma skin cancers or cervical carcinoma in situ).
13. Patient is pregnant or nursing.
14. Patient likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the patient and Investigator's knowledge.
15. Weight >300 pounds

For Aim 1 (Bone biopsy):

1. Allergy to tetracycline or demeclocycline.