Detection of Impaired Intrinsic Bone Strength in vivo by Ultrasound Critical Angle Reflectometry

Study ID
STU 082010-235

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

Contact
Ashlei Johnson-Wilder
214-648-0394
ashlei.johnson@utsouthwestern.edu

Principal Investigator
Khashayar Sakhaee

Summary

Bone mineral density measurements are considered the [Quote]gold standard[Quote] non-invasive method of evaluating and screening for metabolic bone diseases. it is therefore necessary that this measurement (bone density) be done in this study so that we can compare the results obtained using the uCR device (which is still considered an investigational tool) to those obtained by the standard accepted method.
Screening: Women of child-bearing age will be given a pregnancy test prior to any procedures involving radiation. Patients will have spine and hip bone density measurements as standard care. normal volunteers: a bone density of L2-L4 vertebrae and femoral neck by dual photon x-ray absorptiometry will be done. Screening will take approximately 15 minutes and will be performed on the same day as the uCR measurements.
any patient that does not have existing lab values will also have one blood draw for SMa, 25-hydroxy vitamin D and PTH and normal volunteers will have one blood sample drawn for SMa 24 and PTH. The results from the blood tests will not be used to determine eligibility. The amount of blood drawn will be about 4 teaspoons.
Measurement of Bone elasticity in the Heel and tibial shaft: We will use a specialized ultrasound device to perform these tests. The device involves placing a transducer head in contact with the skin just as done in ordinary ultrasound, and measuring the bone elasticity at different positions and angles along the limb, using uCR. Typically the duration of the uCR procedure lasts less than 30 min during each visit.
initial Measurements (aims 1, 2, 3, 4, 8, and 9): uCR of the heel and tibial shaft will be made once in subjects.
Repeat Measurements (aims 5, 6, 7, and 10): in untreated osteoporotic men and women who already had initial uCR measurement, repeat uCR measurements will be made every 6 to 12 months thereafter following treatment with bisphosphonate or parathyroid hormone peptide. in patients in whom treatment with an osteoporosis drug (bisphosphonate, Forteo or neosten) is stopped, repeat uCR measurements will be done at 6 to 12 months after drug withdrawal. among patients in whom bisphosphonate treatment is stopped due to a suspected adynamic bone disease, investigators will have the option of starting Forteo or neosten. investigators will be encouraged to include a control group who are not taking either Forteo or neosten. The number of subjects enrolled will depend on investigators' interest and patient availability.
Validity measurements (aim 11): Measurements for validity of measurements made with the [Quote]research model[Quote] of the uCR device using a newly updated uCR device will be made once in a) 20 normal volunteers, b) 20 patients treated with bisphosphonates and c) 20 subjects who have had a renal transplant. The duration of the uCR procedure will last approximately 30 minutes.
Multiple measurements: uCR measurements will be performed three times within 3 weeks in 14 subjects, including normal women, normal men, untreated osteoporotic women and untreated osteoporotic men.
uCR measurements of the accessible arteries for the visualization of the radial, popliteal, and/or carotid artery will be made once in subjects from groups described in aim 12.

Participant Eligibility

Aims 1 and 2:
Subjects: 500 normal white women and 250 normal white men between 20-80 years of age
Inclusion Criteria: T-score (bone density compared with what is normally expected in a healthy young adult of the same sex) of L2-L4 or L1-L4 bone density > -2.5, or of femoral neck bone density among patients with invalid spinal bone density due to skeletal deformities a T-score of femoral neck > -2.5 with any baseline serum concentration of 25-OHD. Women taking estrogen or selective estrogen receptor modulators will be allowed.

Aim 3:
Subjects: 375 Postmenopausal white women, 40-80 years of age.
Inclusion Criteria: Natural menopause or post-oophorectomy, established osteoporosis, defined by non-traumatic fractures, osteoporosis based on density criteria, with T-score of L2-L4 or L1-L4 spinal bone density of < -2.5, or of femoral neck bone density < -2.5 among patients with invalid spinal bone density due to skeletal deformities. Treatment with estrogen, selective estrogen receptor modulators, or calcium supplements allowed.

Aim 4:
Subjects: 350 white ambulatory premenopausal women or men with osteoporosis, 30-80 years of age, with established osteoporosis.
Inclusion Criteria: Osteoporosis defined by non-traumatic fractures, osteoporosis based on density criteria, with T-score of L2-L4 or L1-L4 spinal bone density of < -2.5, or of femoral neck bone density < -2.5 among patients with invalid spinal bone density due to skeletal deformities. Treatment with estrogen, selective estrogen receptor modulators, or calcium supplements allowed.

Aim 5:
Subjects: 350 white ambulatory women or men 30-80 years of age with osteoporosis on bisphosphonate treatment. Inclusion Criteria: Treatment with estrogen, selective estrogen receptor modulators, or calcium supplements allowed. Treatment with bisphosphonate for 3 months or more, with or without non-spinal recurrent fracture is allowed.

Aim 6:
Subjects: 175 ambulatory white women or men 30-80 years of age with osteoporosis patients taking Forteo for 3 months or more.
Inclusion Criteria: Subjects may be with or without fractures. Treatment with estrogen, selective estrogen receptor modulators, or calcium supplements allowed. Subjects with or without steroid therapy and with or without bisphosphonate therapy may be included.

Aim 7:
Subjects: 70 elderly ambulatory women (> 65 years) with established postmenopausal osteoporosis who are participating in a randomized trial between Neosten 25 mg bid and Fosamax 70 mg/week conducted by Dr. Craig Rubin under IND 20,612.
Inclusion Criteria: elderly ambulatory postmenopausal women (> 65 years) with established postmenopausal osteoporosis randomized to Fosamax 70 mg/week or Neosten 25 mg bid.

Aim 8:
Subjects: 100 ambulatory white women or men 30-80 years of age >= 2 years post-renal transplantation, with stable renal function, with or without fractures post-renal transplantation.
Inclusion Criteria: Treatment with estrogen, selective estrogen receptor modulators, or calcium supplements is allowed. Subjects may be with or without steroid therapy and with or without bisphosphonate therapy.

Aim 9:
Subjects: White women or men 20-80 years of age, with or without fractures, diagnosed with Primary hyperparathyroidism of varying severity, hypoparathyroidism, immobilization, osteogenesis imperfecta, osteomalacia, renal osteodystrophy, osteonecrosis of the jaw, anticonvulsant use, or steroid therapy.
Inclusion Criteria: Subjects will be ambulatory except in immobilization. Treatment with estrogen, selective estrogen receptor modulators, or calcium supplements is allowed.

Aim 10: Any of the above subjects that have begun or stopped therapy of osteoporosis.

Aim 11: Subjects: a) 20 normal postmenopausal white women between 40-80 years of age b) 20 postmenopausal white women between 40-80 years of age on bisphosphonate treatment c) 20 ambulatory white women or men between 30-80 years of age >= 2 years post-renal transplantation
Inclusion Criteria/Exclusion criteria: a) Inclusion - any normal postmenopausal white women between 40-80 years of age will be allowed to participate; Exclusion x Same as for Aims 1 and 2 b) Same as for Aim 5 with additional exclusion for subjects taking Forteo or Neosten c) Same as for

Aim 8
Multiple Measurements:
Subjects: 14 normal and/or untreated osteoporotic men and women.
Inclusion Criteria: Osteoporosis defined by non-traumatic fractures, osteoporosis based on density criteria, with T-score of L2-L4 or L1-L4 spinal bone density of < -2.5, or of femoral neck bone density < -2.5 among patients with invalid spinal bone density due to skeletal deformities.

Aim 12:
Inclusion criteria: Adult patients over the age of 18 of either gender will be recruited from the CKD research clinic in St Paul, the Vascular Access Clinic at Parkland, and from CKD clinics at Parkland, and CKD and access clinics at St Paul.