Treatment of bone disease in cystic fibrosis.

Purpose Of Review: As individuals with cystic fibrosis (CF) have experienced marked improvements in longevity over the last three decades, bone disease has emerged as a new problem. Bone disease in CF has not been previously reviewed in this journal. Therefore, this review will give a brief overview of bone disease in CF and then concentrate on treatment options.

Efficacy of alendronate in adults with cystic fibrosis with low bone density.

As adults with cystic fibrosis (CF) have enjoyed incremental increases in longevity over the last few decades, they have also been suffering from low bone density and its clinical manifestations, fractures and kyphosis. We conducted a placebo-controlled, randomized, double-blinded trial of alendronate (10 mg/day orally) (n = 24) compared with placebo (n = 24) for 1 year in 48 patients to improve bone mineral density at the spine as the primary endpoint. All patients received 800 IU of cholecalciferol and 1,000 mg of calcium carbonate.

Short-term calcitriol administration improves calcium homeostasis in adults with cystic fibrosis.

Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls.

Abnormal bone turnover in cystic fibrosis adults.

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption.

Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients.

Background: Osteoporosis diminishes the quality of life in adults with cystic fibrosis (CF). Vitamin D deficiency resulting from malabsorption may be a factor in the etiology of low bone mineral density (BMD) in patients with CF.

Objective: Absorption of oral ergocalciferol (vitamin D2) and the consequent response of 25-hydroxyvitamin D in 10 adults with CF and exocrine pancreatic insufficiency was compared with that of 10 healthy control subjects.

Adverse alterations in bone metabolism are associated with lung infection in adults with cystic fibrosis.

Low bone density, fractures, and kyphosis complicate the lives of adults with cystic fibrosis (CF), and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) that may alter bone metabolism have been previously found to be increased in the lungs and serum of CF patients. The objective of this prospective study was to determine the impact of lung infection on bone physiology in 17 adult CF patients. Serum osteocalcin, a marker of bone formation; urine N-telopeptides of type I collagen and free deoxypyridinoline, both of which are markers of bone breakdown; serum cytokines (TNF-alpha, IL-1beta, and IL-6); and general inflammatory markers (serum C-reactive protein [CRP] and chondrex) were measured at the beginning and end of treatment for an acute exacerbation of lung infection and again 3 wk later.

Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation.

Lung transplantation with its attendant life-long immunosuppression contributes to bone loss and its sequelae, fractures and kyphosis, in patients with lung disease, many of whom already suffer from severe osteoporosis. Patients with cystic fibrosis (CF) are one of the most severely affected groups. We conducted a controlled, randomized, nonblinded trial of pamidronate (30 mg intravenously every 3 mo) with vitamin D (800 IU/d) and calcium (1 g/d) (n = 16) compared with vitamin D and calcium alone (n = 18, the control subjects) for 2 yr in 34 patients after lung transplant to improve bone mineral density (BMD).

Altered calcium homeostasis in adults with cystic fibrosis.

Bone mineral density (BMD) in cystic fibrosis (CF) patients falls progressively below normal with advancing age, in part due to steroid administration, low levels of sex hormones, chronic inflammatory disease, physical inactivity, and chronic malabsorption of calcium and/or vitamin D. The purpose of this study was to compare the fractional absorption of (45)Ca and urinary excretion of calcium in CF subjects and normal controls following a high-calcium breakfast containing (45)Ca. Seven young men and 5 young women with CF with pancreatic insufficiency were studied on two separate occasions, with and without administration of pancreatic enzymes.

Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis.

Background: Osteoporosis occurs in patients with cystic fibrosis as they age, but its clinical implications are not well defined.

Objective: To determine the clinical effect of decreased bone mineral density in adults with cystic fibrosis and to assess possible clinical predictors of osteoporosis.

Design: Retrospective cohort study.

Severe osteoporosis before and after lung transplantation.

Study Objective: Osteoporosis and/or fractures have been reported as a complication of kidney, heart, liver, bone marrow, and, most recently, lung transplantation (LTx). We measured bone mineral density (BMD) before and after LTx to determine the frequency and severity of preoperative and postoperative osteoporosis.

Patients And Methods: We conducted a cross-sectional study of BMD in 100 patients with various diagnoses before (n = 55) and after (n = 45) LTx.

Parathyroid hormone secretion from dispersed human hyperparathyroid cells: increased secretion in cells from hyperplastic glands versus adenomas.

The in vitro secretion of PTH by dispersed human parathyroid cells was examined under conditions of low and high extracellular Ca+2 using tissue from patients with primary hyperparathyroidism and hyperparathyroidism resulting from chronic renal failure (CRF). The PTH secretion rate (nanograms of PTH per 10(5) cells/h) was lower in adenomatous tissues than in either primary hyperplastic cells or CRF cells under conditions of low (0.5 mM) or high (2.

Divergent effects of forskolin on 3',5' cyclic adenosine monophosphate production and parathyroid hormone secretion.

Forskolin, a diterpene which directly stimulates adenylate cyclase, markedly stimulated cAMP production in intact rat parathyroid glands and dispersed cells from hyperplastic and adenomatous human parathyroid tissues. Stimulation of cAMP production in human parathyroid adenomas occurred as early as 2 min and continued for at least 2 h; furthermore, a dose-response relationship was observed, with a maximal 80-fold cAMP response occurring at 100 microM forskolin. When PTH secretion by rat or human parathyroid tissues was studied at low (0.

Adrenocorticotropin radioimmunoassay: properties of antisera against synthetic ACTH(1-24) and its clinical application.

Two antisera against synthetic ACTH(1-24) developed in rabbit showed strikingly different affinities toward the ACTH molecule. Both antisera (A-6 and A-7) were highly specific for the COOH-terminal region of ACTH(1-24). Antisera A-6 recognized ACTH(1-39) poorly.

Activation of adrenal adenylate cyclase by guanine nucleotides. Promotion of nucleotide binding by calcium but not by adrenocorticotropic hormone.

Calcium ion is essential for normal stimulation of adrenal cortical adenylate cyclase by adrenocorticotropic hormone (ACTH). Both ACTH and Ca2+ act to promote the activation of adenylate cyclase by guanine nucleotides such as guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. To define further the mechanisms by which Ca2+ and ACTH interact with guanine nucleotides, we have correlated the binding of [3H]Gpp(NH)p to adrenal membranes and solubilized membrane proteins with activation of membrane-bound and solubilized adenylate cyclase.

Thyroid venous catheterization in the early diagnosis of familial medullary thyroid carcinoma.

In kindreds with familial medullary thyroid carcinoma (MTC), individuals are often detected whose peripheral plasma calcitonin (CT) levels are undetectable in the basal state but increase minimally following provocative testing. The proper management of such patients has been uncertain, but most investigators have advocated repeat testing and evaluation after an interval of several months. The present study was conducted to evaluate the diagnostic implications of these modest increases in plasma calcitonin.

Magnesium promotes both parathyroid hormone secretion and adenosine 3',5'-monophosphate production in rat parathyroid tissues and reverses the inhibitory effects of calcium on adenylate cyclase.

Reduced extracellular Ca2+ is known to promote PTH secretion, while severe Mg2+ depletion has the opposite effect. We have correlated the effects of Mg2+ and Ca2+ on parathyroid hormone (PTH) secretion and cAMP accumulation by rat parathyroid tissues in vitro with the effects of these two metals on adenylate cyclase activity in broken membrane preparations. PTH secretion was maximal at 0.

Adenylate cyclase activity in human parathyroid tissues: reduced sensitivity to suppression by calcium in parathyroid adenomas as compared with normal glands form normocalcemic subjects or noninvolved glands from hyperparathyroid subjects.

To examine whether alterations in parathyroid adenylate cyclase might be associated with glandular hyperfunction, we compared enzyme activity in membranes from 7 normal glands with activity from 18 abnormal and 5 noninvolved glands from patients with primary hyperparathyroidism. Compared with the normal glands, the specific enzyme activity after full stimulation with guanyl-5'yl imidodiphosphate was significantly decreased in both hyperplastic and noninvolved glands from the hyperparathyroid subjects. While the enzyme activity of all tissues could be suppressed by calcium, a twofold higher calcium concentration was required for comparable suppression of the enzyme from adenomas as compared with normal or noninvolved glands.