Treatment of Low Bone Density in Cystic Fibrosis.

Condition(s) targeted: Osteoporosis; Cystic Fibrosis

Intervention: Alendronate (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Istituto Auxologico Italiano

Official(s) and/or principal investigator(s):
Maria Luisa Bianchi, M.D., Principal Investigator, Affiliation: Istituto Auxologico Italiano

Cystic fibrosis (CF) - - an autosomal recessive genetic disease affecting about 60,000

individuals worldwide, including about 3,800 in Italy - - is often associated with low bone

mineral mass. The current aggressive therapies have ensured a much longer survival of CF patients but this has led to a higher frequency of osteoporosis and bone fractures, a serious problem which not only affects quality of life, but also hinders further therapeutic measures. The aim of this study, conducted on a large group of children, adolescents and young adults with CF, has been the evaluation of bone mass changes after 1 year of a simple treatment with RDA-adjusted dietary calcium plus 25-OH vitamin D supplementation, and the feasibility and efficacy of alendronate treatment (for another year) in patients not responding to calcium + 25-OH vitamin D alone.

Official title: Osteoporosis in Cystic Fibrosis: Study of Bone Mass and Bone Metabolism, and Prospective Randomized Therapeutic Trial.

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Bone mineral density increase at lumbar spine.

Secondary outcome:

Changes in bone turnover markers.

Fracture rate.

Adverse effects of alendronate.

Detailed description: The study included 2 phases. Phase 1 (1-year open-label observational study): following baseline evaluation, bone mass changes have been studied with a simple therapy of adequate calcium intake and 25-OH vitamin D supplements in all eligible subjects (N=171). Phase 2 (1-year double-blind, randomized, placebo-controlled, parallel group study): the 128 subjects showing an insufficient response to calcium + 25-OH vitamin D alone (bone mass increase <5%) at the end of Phase 1, were randomized into 2 groups and assigned to alendronate treatment (N=65) or placebo (N=63) (in addition to calcium and 25-OH vitamin D as during Phase 1). The study has been carried out by the Coordinator's Institution (Istituto Auxologico Italiano)in collaboration with most Regional Reference Centers for CF in Italy.

Minimum age: 5 Years. Maximum age: 30 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- age 2-30 years

- clinically stable condition

- regular menses in females

- low Bone Mineral Apparent Density for age (defined as BMAD Z-score ≤-2. 0 if age ≤18

years or ≤-2. 5 if age >18 years). Exclusion Criteria:

- two or more episodes of hypercalcemia and/or hypercalciuria

- contraindications to 25-OH vitamin D or alendronate treatment

- recent transplantation

- other diseases or medications (glucocorticoids excepted) associated with bone loss.

CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù, Città del Vaticano, Holy See (Vatican City State)

CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia, Grosseto, Italy

CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina, Messina, Italy

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy

Istituto Auxologico Italiano IRCCS, Milano 20145, Italy

CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II, Napoli, Italy

CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy

CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico, Palermo, Italy

CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I, Roma, Italy

CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo, Trieste, Italy

CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona, Verona, Italy

Study protocol

Lab test information

Related publications:

Grey AB, Ames RW, Matthews RD, Reid IR. Bone mineral density and body composition in adult patients with cystic fibrosis. Thorax. 1993 Jun;48(6):589-93.

Henderson RC, Madsen CD. Bone density in children and adolescents with cystic fibrosis. J Pediatr. 1996 Jan;128(1):28-34.

Bhudhikanok GS, Lim J, Marcus R, Harkins A, Moss RB, Bachrach LK. Correlates of osteopenia in patients with cystic fibrosis. Pediatrics. 1996 Jan;97(1):103-11.

Baroncelli GI, De Luca F, Magazzú G, Arrigo T, Sferlazzas C, Catena C, Bertelloni S, Saggese G. Bone demineralization in cystic fibrosis: evidence of imbalance between bone formation and degradation. Pediatr Res. 1997 Mar;41(3):397-403.

Humphries IR, Allen JR, Waters DL, Howman-Giles R, Gaskin KJ. Volumetric bone mineral density in children with cystic fibrosis. Appl Radiat Isot. 1998 May-Jun;49(5-6):593-5.

Aris RM, Renner JB, Winders AD, Buell HE, Riggs DB, Lester GE, Ontjes DA. Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. Ann Intern Med. 1998 Feb 1;128(3):186-93.

Bhudhikanok GS, Wang MC, Marcus R, Harkins A, Moss RB, Bachrach LK. Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study. J Pediatr. 1998 Jul;133(1):18-27.

Henderson RC, Madsen CD. Bone mineral content and body composition in children and young adults with cystic fibrosis. Pediatr Pulmonol. 1999 Feb;27(2):80-4.

Bianchi ML, Cimaz R, Bardare M, Zulian F, Lepore L, Boncompagni A, Galbiati E, Corona F, Luisetto G, Giuntini D, Picco P, Brandi ML, Falcini F. Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study. Arthritis Rheum. 2000 Sep;43(9):1960-6.

Brumsen C, Hamdy NA, Papapoulos SE. Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Medicine (Baltimore). 1997 Jul;76(4):266-83. Review.

Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998 Oct 1;339(14):947-52.

Starting date: October 2002
Last updated: March 5, 2014