TOP: Recombinant Human Parathyroid Hormone (ALX1-11) on Fracture Incidence in Women With Postmenopausal Osteoporosis
- Registration Number
- NCT00172081
- Lead Sponsor
- Shire
- Brief Summary
This is an 18-month, double-blind, placebo-controlled, Phase III trial with a 12-month interim analysis of the effect of ALX1-11, recombinant human parathyroid hormone (1-84) (rhPTH \[1-84\]), on fracture incidence in women with postmenopausal osteoporosis, the TOP study.
- Detailed Description
Parathyroid hormone (PTH), a polypeptide consisting of 84 amino acids that is synthesized and secreted by the parathyroid glands, is a principal regulator of calcium homeostasis through concerted action on kidney, intestine and bone. Parathyroid hormone exerts its action on bone to release calcium into the extracellular fluid as a process of bone remodeling and also to maintain the serum calcium concentration, but the exact mechanisms are not fully understood. In some circumstances, PTH may exert an anabolic action on bone and can stimulate osteoblast proliferation and mature osteoblast function. The net effect of exogenous PTH administration on bone turnover depends on the pattern of delivery. A continuous long-term infusion gives a net decrease in trabecular bone volume, whereas daily single injections result in a net increase.
NPS Allelix Corp. is developing ALX1-11, recombinant human parathyroid hormone (1-84), for the treatment of osteoporosis. ALX1-11 is identical to the endogenous intact 84 amino acid human hormone and will be self-administered on a daily basis by subcutaneous (sc) injection.
Currently, there is no approved therapy for osteoporosis capable of stimulating the formation of new bone of normal composition and structure. Most therapies in development are anti-catabolic and only prevent further bone loss (e.g., estrogen replacement, bisphosphonates, and calcitonins). ALX1-11 has the potential to stimulate new bone formation in osteoporotic patients, thereby increasing bone mass and preventing fractures. Patients with moderately or severely reduced bone density and a fracture would be expected to benefit from treatment, thereby improving functional status and alleviating symptoms.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 2532
-
Women who are postmenopausal with at least one year since the last menstruation.
-
Women who are 45-54 years of age with the following bone mineral density (BMD) and/or vertebral fracture:
- BMD 3.0 standard deviations (SDs) or more below peak bone mass of young females at the lumbar spine, femoral neck, or total hip; or
- BMD 2.5 SDs or more below peak bone mass of young females at the lumbar spine, femoral neck or total hip with the presence of a vertebral fracture verified by the central imaging organization before the patient is enrolled into the study.
-
Women 55 or more years of age with the following BMD and/or vertebral fracture:
- BMD 2.5 SDs or more below peak bone mass of young females at the lumbar spine, femoral neck or total hip; or
- BMD 2.0 SDs or more below peak bone mass of young females at the lumbar spine, femoral neck or total hip with the presence of a vertebral fracture verified by the central imaging organization before the patient is enrolled into the study.
-
The following types of vertebral fractures should not be considered for patient enrollment into this trial:
- Pathological fractures due to malignant disease or infection
- Fractures due to excessive trauma sufficient to cause a fracture in young individuals with normal bone mass
-
Women with the ability to self-administer a daily injection or have a designee who will give the injections
-
Women who are capable of understanding and giving written, voluntary informed consent before the clinical trial screening visit
A. Vertebral Deformity:
- Patient has 5 or more vertebral (thoracic and lumbar) deformities
- Patient has 2 or more lumbar vertebral deformities (L1 to L4)
- Severe lumbar scoliosis (>15 degrees) which precludes a reliable evaluation of the dual x-ray absorptiometry (DXA)
B. DXA Imaging:
- Inability to have a DXA scan performed.
C. History or Concurrent Illness:
- Disorders of immunity
- Endocrine system
- Gastrointestinal system
- Kidney and collecting system
- Liver, biliary tract and pancreatic systems
- Musculoskeletal system
- Neoplasia
- Nervous system
- Vascular, respiratory and cardiac system
- Significant diseases or disorders are determined by history, physical exam or laboratory screens and judged by the Principal Investigator to be significant.
D. Concurrent Medication:
Any patient who does not require medication washout (discontinuation) as specified below may start study drug dosing after 2 weeks of stabilization treatment with calcium and vitamin D3 supplements. All exceptions will be documented in the case report form (CRF).
-
Patients cannot be enrolled into this clinical trial if they have received any of the following therapies at any time:
- Any PTH or PTH analogs [e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs]
- Fluoride
- Strontium
-
Patients must have been off the following agents for the specified times before entering the screening phase of this clinical trial:
-
Any investigational drug (30 days)
-
Anabolic steroids or androgens (6 consecutive months)
-
Active vitamin D3 metabolites and analogs(90 days)
-
Systemic corticosteroids, more than 5 mg/day prednisone or a systemic corticosteroid formulation equivalent to 5 mg/day prednisone (12 consecutive months).
-
A patient who has been enrolled in the study and needs to receive an acute bolus of steroids (oral or injectable) for a self-limited illness may continue treatment in the study if the following requirements are met:
- Exposure to steroids is limited to no more than 30 consecutive days
- The maximal dose of steroid (prednisone equivalent) is limited to no more than 225 mg (7.5 mg each day for 30 days)
- The illness is acute in nature and is not expected to recur during the remaining treatment period of the study
-
Daily inhaled corticosteroids unless dose is below 1200 mg/day of beclomethasone.
-
Bisphosphonates, including investigational bisphosphonates.
-
Intravenous (IV) pamidronate. Patient must be receiving pamidronate specifically to treat osteoporosis. Patient can have received only ONE IV dose of pamidronate in the 12 months immediately preceding the screening visit.
-
Cyclical etidronate. Exposure to cyclical etidronate must be less than or equal to 6 months on a standard dose (e.g. 400 mg/day). Patient should not have exposure to cyclical etidronate for 9 months prior to the screening visit.
-
Phenytoin for seizure control. If the patient has received phenytoin within five years of the screening visit, the patient is excluded from this study. The patient may continue in the screening process if 15 years have passed since the last dose of phenytoin at the time of the screening visit. If the phenytoin use was between 5-15 years before the screening visit and the patient received phenytoin for less than 2 months.
-
-
Patients may be enrolled if they have been stabilized on the following therapy for the specified amount of time:
* Thyroid hormone (<0.1 mg/day thyroxine) therapy for at least 6 months. * Stable dosage of thiazide for at least 3 consecutive months.
-
All patients must stop the following therapies at least 4 weeks prior to the screening visit and remain off these therapies for the remainder of the clinical trial. Screening laboratories must be performed after the washout is complete. However, imaging studies (BMD, X-rays) may be performed prior to starting the calcitonin, estrogen, and selective estrogen receptor modulation (SERM) washout.
- Calcitonin
- Estrogen replacement therapy by oral, transdermal or intramuscular administration
- SERM drugs, e.g., tamoxifen, raloxifene, Evista
- Vaginal application of estrogen-containing creams unless the dose is conjugated estrogen or estradiol* Cytostatics, e.g., azathioprine, recombinant human tumor necrosis fusion (Fc) protein, monoclonal antibody against tumor necrosis factor (e.g., remicade [infliximab])
- The drug class tetracyclines
- Medication known to affect the metabolism of bone (the Principal Investigator should discuss this with the Project Medical Officer before the patient is excluded from enrollment)
E. Miscellaneous Concurrent Medications:
- Methotrexate
- Intra-articular injections - Patients with chronic, active joint disease should be excluded from this Phase III study. Patients may receive a maximum of one intra-articular injection (ONE JOINT ONLY) every 6 months while participating in this Phase III study. The dose of corticosteroid injected should not exceed the anti-inflammatory equivalent dose of prednisone 40 mg suspension. The dose and volume should be adjusted downward as appropriate to the size of the joint.
- Provera is an acceptable concomitant medication when used according to the label instructions.
F. Laboratory Values and Physical Examination Findings:
-
Serum calcium greater than 10.7 mg/dL (2.66 mmol/L). At screening, if the serum calcium is abnormal, the patient may have the additional evaluation described below ONCE:
- Discontinue all oral calcium and vitamin D3 supplements.
- Repeat a fasting serum calcium level two weeks later.
- If the fasting serum calcium level is still abnormal, the patient is discontinued from the study.
- If the repeat fasting serum calcium is normal, the patient should have supplemental calcium and vitamin D3 restarted at the time of study drug dosing, without going through a two-week stabilization period.
-
Serum creatinine > 1.5 mg/dL (132.6 mmol/L)
-
Urinary calcium to creatinine ratio is greater than or equal to 1. At screening, if a patient's urinary calcium to creatinine ratio is abnormal, the patient may have the additional evaluation described below ONCE:
- Discontinue all oral calcium and vitamin D3 supplements.
- Repeat a fasting urine calcium to creatinine ratio two weeks later.
- If the fasting urinary calcium to creatinine ratio is still abnormal, the patient is discontinued from the study.
- If the repeat fasting urinary calcium to creatinine ratio is normal, the patient should have supplemental calcium and vitamin D3 restarted at the time of study drug dosing, without going through a two-week stabilization period.
-
Total serum alkaline phosphatase >130 U/L except as noted - Argentina (311 U/L); Brazil (278 U/L); Mexico (159 U/L).
-
Any other clinically significant abnormal value as judged by the investigator
-
Body weight below 40 kg
G. Substance Abuse:
- Alcohol and/or drug abuse
H. Psychiatric Disease:
- Current or history of psychiatric disease that would interfere with the ability to comply with the clinical trial protocol
I. Compliance:
- Suspected or confirmed poor compliance in completing clinical trial evaluations and/or clinical trial required questionnaires
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo placebo Daily subcutaneous injection into thigh or abdomen with 700 mg Calcium and 400 IU Vitamin D daily PTH(1-84) 100 mcg ALX1-11 Subcutaneous injection of PTH(1-84) with 700 mg Calcium and 400 IU Vitamin D daily
- Primary Outcome Measures
Name Time Method Compare effects of 18 months of treatment with ALX1-11/placebo on the incidence of new and/or worsened thoracic and lumbar vertebral fractures in postmenopausal women with osteoporosis receiving calcium and vitamin D3 supplements At Month 18
- Secondary Outcome Measures
Name Time Method Incidences of vertebral fractures at Month 12; hip and wrist fractures; and other clinical fractures. At Month 12
Trial Locations
- Locations (168)
'East Bay Clinical Trial Center
🇺🇸Concord, California, United States
'Community Research Centers
🇺🇸Santa Ana, California, United States
Rush-Prebyterian-St.Luke's Medical Center
🇺🇸Chicago, Illinois, United States
'The University of Chicago
🇺🇸Chicago, Illinois, United States
'Maine Center for Osteoporosis Research & Education
🇺🇸Bangor, Maine, United States
'Phase III Clinical Research
🇺🇸Fall River, Massachusetts, United States
'Comprehensive Clinical Research
🇺🇸Berlin, New Jersey, United States
'Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
'Osteoporosis Center
🇺🇸Medford, Oregon, United States
'Radiant Research/Dallas
🇺🇸Dallas, Texas, United States
'Sunnybrook and Women's College Health Science Center
🇨🇦Toronto, Ontario, Canada
Phillip J. Mease
🇺🇸Seattle, Washington, United States
'Osteoporosis Research Group
🇺🇸Seattle, Washington, United States
'Breco Research Inc.
🇺🇸Houston, Texas, United States
'Florida Wellcare Alliance
🇺🇸Inverness, Florida, United States
'Centro Médico T.I.E.M.P.O
🇦🇷Buenos Aires, BUE, Argentina
'Salt Lake Women's Center
🇺🇸Sandy, Utah, United States
'Universidade Federal de São Paulo
🇧🇷Sao Paulo, SP, Brazil
'Heritage Medical Research Clinic
🇨🇦Calgary, Alberta, Canada
'Centre d'Etude Clinique Montreal Inc.
🇨🇦Montreal, Quebec, Canada
'St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
'Riverside Medical Centre
🇨🇦Charlottetown, Prince Edward Island, Canada
'Osteoporosis Center University of Miami
🇺🇸Miami, Florida, United States
'University Hospital & Outpatient Center
🇺🇸Indianapolis, Indiana, United States
'VA Southern NV Healthcare Systems
🇺🇸Las Vegas, Nevada, United States
'Duke University Medical Center
🇺🇸Durham, North Carolina, United States
'Diabetes & Glandular Disease Research Associates, P.A.
🇺🇸San Antonio, Texas, United States
'Radiant Research San Antonio
🇺🇸San Antonio, Texas, United States
'Universidade Federal de Pernambuco
🇧🇷Recife, PE, Brazil
'Clalit Health Services
🇮🇱Beer Sheva, Israel
'Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
'Wichita Clinic
🇺🇸Wichita, Kansas, United States
Michael J. Lillestol
🇺🇸Fargo, North Dakota, United States
'Odyssey Research Services
🇺🇸Minot, North Dakota, United States
'Altru Health Systems/Altru Research Center
🇺🇸Grand Forks, North Dakota, United States
'Manitoba Clinic
🇨🇦Winnipeg, Manitoba, Canada
'Radiant Research - Phoenix
🇺🇸Phoenix, Arizona, United States
'San Francisco General Hospital
🇺🇸San Francisco, California, United States
'Michigan Bone & Mineral Clinic
🇺🇸Detroit, Michigan, United States
Capstone Clinical Trials
🇺🇸Birmingham, Alabama, United States
'The University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
'Denver Arthritis Clinic
🇺🇸Denver, Colorado, United States
'Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
'Rheumatology Associates of North Alabama
🇺🇸Huntsville, Alabama, United States
'Robin K. Dore, M.D., Inc.
🇺🇸Anaheim, California, United States
'Osteoporosis Medical Center
🇺🇸Beverly Hills, California, United States
'Desert Medical Advances
🇺🇸Palm Desert, California, United States
'Loma Linda Osteoporosis Research Center
🇺🇸Loma Linda, California, United States
'The Foundation for Osteoporosis Research and Education
🇺🇸Oakland, California, United States
'Radiant Research - San Diego
🇺🇸San Diego, California, United States
'VA Palo Alto Health Care System
🇺🇸Palo Alto, California, United States
'Boling Clinical Trials
🇺🇸Rancho Cucamonga, California, United States
'S.D. Arthritis & Osteoporosis Medical Clinic
🇺🇸San Diego, California, United States
'Colorado Center for Bone Research
🇺🇸Lakewood, Colorado, United States
'Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
'ICSL Clinical Studies
🇺🇸Saint Petersburg, Florida, United States
'Longmont Medical Research Network
🇺🇸Longmont, Colorado, United States
'RASF - Clinical Research Center
🇺🇸Boca Raton, Florida, United States
'Northeast Clinical Research, LLC
🇺🇸Hamden, Connecticut, United States
'The Center for Diabetes and Endocrine Care
🇺🇸Hollywood, Florida, United States
'Renstar Medical Group
🇺🇸Ocala, Florida, United States
'Radiant Research - Lake Worth
🇺🇸Lake Worth, Florida, United States
'The Arthritis Center
🇺🇸Palm Harbor, Florida, United States
'Diabetes and Endocrinology Treatment Center
🇺🇸Palm Beach Gardens, Florida, United States
'The Centre for Arthritis and Rheumatic Diseases
🇺🇸South Miami, Florida, United States
'Palm Beach Research Center
🇺🇸West Palm Beach, Florida, United States
'Radiant Research - Stuart & LakeWorth
🇺🇸Stuart, Florida, United States
'The Emory Clinic
🇺🇸Atlanta, Georgia, United States
'Intermountain Orthopaedics
🇺🇸Boise, Idaho, United States
'Radiant Research
🇺🇸Greer, South Carolina, United States
'ICSL-Clinical Studies
🇺🇸Bloomington, Illinois, United States
'Mercy Arthritis and Osteoporosis Center
🇺🇸Des Moines, Iowa, United States
'Ochsner Clinic
🇺🇸New Orleans, Louisiana, United States
'Bethesda Health Research Center
🇺🇸Bethesda, Maryland, United States
'The Osteoporosis and Clinical Trials Center
🇺🇸Hagerstown, Maryland, United States
'Arthritis & Osteoporosis Center of Maryland
🇺🇸Frederick, Maryland, United States
'Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
'The Center for Rheumatology and Bone Research
🇺🇸Wheaton, Maryland, United States
'Osteoporosis Research & Treatment Center
🇺🇸Worcester, Massachusetts, United States
'Desoto Family Medical Center
🇺🇸Olive Branch, Mississippi, United States
'Arthritis, Osteoporosis Muscle Skeletal Disease Center
🇺🇸Concord, New Hampshire, United States
'New Mexico Clinical Research and Osteoporosis Center
🇺🇸Albuquerque, New Mexico, United States
'Anderson and Collins Clinical Research Inc.
🇺🇸South Plainfield, New Jersey, United States
'Rochester Clinical Research Inc.
🇺🇸Rochester, New York, United States
'Bone Mineral Research Center
🇺🇸Mineola, New York, United States
'Lovelace Scientific Resources
🇺🇸Albuquerque, New Mexico, United States
'Beth Israël Medical Center
🇺🇸New York, New York, United States
'College of Physicians and Surgeons, Columbia University
🇺🇸New York, New York, United States
'Physicians Clinical Research Services
🇺🇸White Plains, New York, United States
'David R. Mandel M.D. Inc.
🇺🇸Mayfield, Ohio, United States
'Oklahoma Center for Arthritis Therapy & Research, Inc.
🇺🇸Tulsa, Oklahoma, United States
'Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
'University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
'Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
'Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
'Clinical Research Center of Reading LLP
🇺🇸West Reading, Pennsylvania, United States
'Roger Williams Medical Center
🇺🇸Providence, Rhode Island, United States
'Rapid City Medical Center
🇺🇸Rapid City, South Dakota, United States
'Averna Research Institute
🇺🇸Sioux Falls, South Dakota, United States
'Clinsearch
🇺🇸Chattanooga, Tennessee, United States
'Brown Clinic
🇺🇸Watertown, South Dakota, United States
'Diabetes Center of the Southwest
🇺🇸Midland, Texas, United States
'Fletcher Allan Health Center, UHC Campus 1
🇺🇸Burlington, Vermont, United States
'National Clinical Research, Inc.
🇺🇸Richmond, Virginia, United States
'Center for Arthritis and Diabetes
🇺🇸Newport News, Virginia, United States
'MCV Physicians Program for Osteoporosis
🇺🇸Richmond, Virginia, United States
'South Puget Sound Clinical Research Center
🇺🇸Olympia, Washington, United States
'University of Wisconsin Medical Foundation
🇺🇸Madison, Wisconsin, United States
'IDIM
🇦🇷Buenos Aires, BUE, Argentina
'Hospital Ramos Mejía
🇦🇷Buenos Aires, BUE, Argentina
'Centro de Osteopatias Medicas
🇦🇷Capital Federal, CBA, Argentina
'Universidade Federal do Paraná
🇧🇷Curitiba, PR, Brazil
'Hospital do Servidor Público do Rio de Janeiro
🇧🇷Rio de Janeiro, RJ, Brazil
'Hospital Santa Casa de Misericórdia do Rio de Janeiro
🇧🇷'Rio de Janeiro, RJ, Brazil
'UNICAMP
🇧🇷Campinas, SP, Brazil
'Hospital Santa Casa de Misericórdia de São Paulo
🇧🇷Sao Paulo, SP, Brazil
'Pontifícia Universidade Católica de Campinas
🇧🇷Campinas, SP, Brazil
'Instituto de Saúde e Bem Estar da Mulher
🇧🇷Sao Paulo, SP, Brazil
'Hospital Heliópolis
🇧🇷Sao Paulo, SP, Brazil
'Multifunctional Hospital for Active Treatment "Sv.Georgy"
🇧🇬Plovdiv, Bulgaria
'Royal Victoria Hospital
🇨🇦Montreal, Ontario, Canada
'SHATENG"Acad.Ivan Penchev"
🇧🇬Sofia, Bulgaria
'Multifunctional Hospital for Active Treatment "Alexandrovska
🇧🇬Sofia, Bulgaria
'Multifunctional Hospital for Active Treatment "Sv.Ivan Rilsky"
🇧🇬Sofia, Bulgaria
'SHATGO"Sheynovo"
🇧🇬Sofia, Bulgaria
St. Joseph's Health Centre
🇨🇦London, Ontario, Canada
Charlton Medical Centre
🇨🇦Hamilton, Ontario, Canada
Osteoporosis Research Center
🇨🇦Vancouver, British Columbia, Canada
'Centre for Activity and Aging
🇨🇦London, Ontario, Canada
Rafat Faraawi
🇨🇦Kitchener, Ontario, Canada
Oakville Bone Center
🇨🇦Oakville, Ontario, Canada
'Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Jude F. Rodrigues
🇨🇦Windsor, Ontario, Canada
'Osteoporosis Research Program
🇨🇦Toronto, Ontario, Canada
'Complexe Hospitalier de la Sagami
🇨🇦Chicoutimi, Quebec, Canada
'Centre de Recherche du CHUM - Hopital Saint-Luc
🇨🇦Montreal, Quebec, Canada
Novabyss Research Clinic
🇨🇦Sherbrooke, Quebec, Canada
Centre de Recherche - CORQ
🇨🇦Sainte-Foy, Quebec, Canada
'Soroka Medical Center
🇮🇱Beer Sheva, Israel
'Saskatoon Osteoporosis Centre
🇨🇦'Saskatoon, Saskatchewan, Canada
'Rambam Medical Center
🇮🇱Haifa, Israel
'Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
'Lin Medical Center
🇮🇱Haifa, Israel
'Hadassah University Hospital
🇮🇱Jerusalem, Israel
'Rabin Medical Center
🇮🇱Petach Tikva, Israel
'Lis Maternity Hospital
🇮🇱Tel Aviv, Israel
'Hospital Clinical del Parque
🇲🇽Chihuahua, Chih, Mexico
'Osteosol
🇲🇽Mexico, DF, Mexico
'Hospital de Mexico
🇲🇽Mexico, DF, Mexico
'Hospital Angeles de las Lomas
🇲🇽'Huixquilucan, Emex, Mexico
'Instituto Mexicano de Investigacion Clinica
🇲🇽Mexico, DF, Mexico
'OPD Hospital Civil de Guadalajara Dr. Juan I. Menchaca
🇲🇽Guadalajara, JAL, Mexico
'Hospital Aranda de la Parra
🇲🇽Leon, GTO, Mexico
'Hospital Civil de Belem
🇲🇽Guadalajara, JAL, Mexico
'Medica Monraz
🇲🇽Guadalajara, JAL, Mexico
'Hospital Central "Ignacio Morones Prieto"
🇲🇽'San Luis Potosi, SLP, Mexico
'Hospital Universitario de Monterrey
🇲🇽Monterrey Nuevo Leon, Mexico
'CLINTRIAL "DORIS" Medical Centre
🇷🇴Bucuresti, Romania
'Centrul Medical Sabyc
🇷🇴Bucuresti, Romania
'Spitalul Clinic Judetean Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
'Scientific Center of Endocrinology of RAMS
🇷🇺Moscow, Russian Federation
'JK "Medicine"
🇷🇺Moscow, Russian Federation
'Russian Academy for Advanced Medical Studies
🇷🇺Moscow, Russian Federation
'Stony Brook Clinical Research Trials Center
🇺🇸Stony Brook, New York, United States
'Columbia Arthritis Center, PA
🇺🇸Columbia, South Carolina, United States
'St. John's Medical Research Group
🇺🇸Springfield, Missouri, United States
'Carolina Bone and Joint - Charlotte
🇺🇸Charlotte, North Carolina, United States