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J P Bilezikian

Publications and source records attributed to J P Bilezikian.

At least 19 recordsLinked to original sources
PubMed2006

Determinants of bone mineral density in Chinese-American women.

SUMMARY: Few data are available regarding bone mineral density (BMD) and its determinants among Chinese Americans. We identified determinants of BMD among 359 Chinese-American women in order to identify risk factors for low BMD in this burgeoning population. BMD in Chinese-American women is influenced by a number of factors, including immigration. INTRODUCTION: Osteoporosis and low BMD are common among Chinese women, including Chinese Americans, who are a growing population at risk for osteoporosis in the US. Few data are available regarding BMD and its determinants among Chinese-American women. METHODS: In this study, we examined predictors of BMD in 359 ambulatory Chinese-American women, ages 20-90, using stepwise multiple regression analysis. Variables in the model included age, weight, height, menarche age, years since menopause, immigration age, years in US, percentage of life in US, number of pregnancies, oral contraceptive use, family history of osteoporosis, family history of hip fracture, daily calcium intake, exercise, time outdoors, alcohol consumption and tobacco use. RESULTS: Among premenopausal women, weight was the strongest predictor of BMD, accounting for 10.5% of the variance at the lumbar spine (LS), 15.2% at the total hip (TH) and 16.6% at the femoral neck (FN). Time outdoors was also a positive predictor of BMD (1.4% at LS, 2.8% at TH and 1.6% at FN), while family history of osteoporosis (1.4% at TH) and age (3.7% at FN) were negative predictors. Among postmenopausal women, greater BMD at the LS and TH was associated with greater weight and earlier immigration age. Weight accounted for 16.4% of the variance at the LS and 19.8% at the TH; immigration age accounted for 3.1% of the variance at the LS and 4.1% at the TH. At the FN, years since menopause and weight were predictors of BMD, accounting for 14.4% and 8.7% of the variance, respectively. While older age at immigration had a negative effect on BMD, years in and proportion of life in the United States were not significant predictors of BMD. CONCLUSIONS: Bone mineral density in Chinese-American women is influenced by a number of biological and lifestyle factors, including immigration. The results of this study provide new insights into risk factors for low bone density as they relate to environmental determinants in the growing population of Chinese-American women.

Adult↗
PubMed2006

A referent bone mineral density database for Chinese American women.

INTRODUCTION: While osteoporosis is common among women of Chinese descent, a readily available bone mineral density (BMD) referent database for Chinese American women does not exist. Fracture risk among this population is currently assessed using a Caucasian reference as well as diagnostic criteria for osteoporosis developed for postmenopausal Caucasian women. Many studies indicate that there are important racial differences in skeletal health and fracture risk, an observation that makes the application of Caucasian data to all groups problematical. This study was undertaken to establish a BMD referent database in Chinese American women and to compare it with a Caucasian female database. It is expected that a race-specific database will be useful in the assessment of bone health for Chinese American women. METHODS: Healthy Chinese American women (n=359), ages 20-90, were recruited. Along with dual-energy X-ray absorptiometry (DXA) of the total hip and lumbar spine, demographic, medical, familial, nutritional, and behavioral data were obtained. The mean and standard deviation for BMD at each site was calculated for each 10-year age group and compared to mean BMD values for Caucasian women supplied as found in the Hologic DXA instrument. Osteoporosis diagnosis rates for this cohort, calculated with the Caucasian and newly established Chinese American BMD referent values, were compared with each other. RESULTS: Compared with Caucasian women, Chinese American women have significantly lower BMD at the lumbar spine, total hip, and femoral neck across a wide spectrum of age groups. As a consequence, more than one-half of Chinese American women>or=50 years of age, who would be characterized as osteoporotic using a Caucasian referent, would not be diagnosed as such if a Chinese American referent were utilized. CONCLUSION: Chinese American reference BMD values are significantly lower than those for Caucasian women. Future studies relating Chinese American BMD values to fracture risk are necessary in order to determine if ethnic database-derived T-scores would be more predictive of fracture risk and to develop meaningful diagnostic criteria for this population.

Absorptiometry, Photon↗
PubMed2006

Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis.

CONTEXT: Treatment of osteoporotic women with PTH increases biochemical markers of bone turnover, increases axial bone mineral density (BMD), and reduces fracture risk. OBJECTIVE: Our objective was to determine the relationship between levels of baseline turnover before PTH therapy and short-term changes in turnover during PTH therapy and subsequent changes in areal and volumetric BMD. DESIGN AND SETTING: We conducted a randomized, placebo-controlled trial at four academic centers. PATIENTS: Patients included 238 postmenopausal women with low hip or spine BMD. INTERVENTION: Subjects were randomized to sc PTH (1-84), 100 mug/d (119 women), for 1 yr. MAIN OUTCOME MEASURE: Bone turnover markers were measured in fasting blood samples collected before therapy and after 1 and 3 months. Areal and volumetric BMD at the spine and hip were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy. RESULTS: Among women treated with PTH alone, the relationships between baseline turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were inconsistent. Greater 1- and 3-month increases in turnover, particularly the formation marker N-propeptide of type I collagen, were associated with greater increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT, greater short-term increases in turnover were even more positively associated with 1-yr increases in BMD. Each sd increase in the 3-month change of N-propeptide of type I collagen was associated with an a 21% greater increase in QCT spine trabecular BMD. CONCLUSIONS: Greater short-term changes in turnover with PTH therapy are associated with greater 1-yr increases in spine and hip BMD among postmenopausal osteoporotic women.

Absorptiometry, Photon↗
PubMed2005

Primary hyperparathyroidism: new concepts in clinical, densitometric and biochemical features.

Primary hyperparathyroidism (PHPT) is characterized most commonly now as an asymptomatic disorder with hypercalcaemia and elevated levels of parathyroid hormone (PTH). The elevation in PTH is detected by both the standard immunoradiometric assays (IRMA) and a more recent IRMA that detects only the 1-84 full-length PTH molecule. The serum calcium concentration is usually <1 mg dL(-1) above normal. Recently, another variant of PHPT (normocalcaemic PHPT) has been described in which the serum calcium is normal but the serum PTH is elevated, in the absence of any secondary cause for PTH elevation. Although usually sporadic, PHPT also occurs in inherited syndromes. Skeletal manifestations are appreciated by densitometry showing a typical pattern in which cancellous bone of the lumbar spine is reasonably well preserved whilst the cortical bone of the distal third of the radius is preferentially reduced. Although reduced in incidence, renal stones remain the most common overt complication of PHPT. Other organs are theoretical targets of PHPT such as the neurobehavioural axis and the cardiovascular system. Vitamin D looms as an important determinant of the activity of the PHPT state. The 2002 NIH Workshop on asymptomatic PHPT has led to revised guidelines to help doctors determine who is best advised to have parathyroid surgery and who can be safely followed without surgery. New information about the natural history of PHPT in those who did not undergo surgery has helped to define more precisely who is at-risk for complications. At the NIH workshop, a number of items were highlighted for further investigation such as pharmacological approaches to controlling hypercalcaemia, elevated PTH levels and maintaining bone density.

Bone Density↗
PubMed2005

Parathyroid hormone as an anabolic therapy for women and men.

The quest for effective treatment of osteoporosis merits great attention because of the widespread, worldwide prevalence of this disease. Antiresorptive drugs reduce bone turnover, increase bone density and improve other aspects of bone quality. This article concentrates on another approach, namely the use of anabolic therapy in which the prospects for improving bone quality are even greater. Parathyroid hormone is available as the aminoterminal fragment, PTH(1-34), known as teriparatide, and is being studied in its full-length form, PTH(1-84). Teriparatide improves bone quality by actions on bone turnover, bone density, bone size and microarchitecture. In women, teriparatide reduces both vertebral and non-vertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the ability of PTH to increase bone density may be reduced. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of parathyroid hormone alone. In order to maintain the densitometric gains in bone density with parathyroid hormone, it is important to follow its use with an antiresorptive agent.

Anabolic Agents↗
PubMed2001

Therapy of male osteoporosis with parathyroid hormone.

Definable causes of male osteoporosis account for only about 60% of the osteoporotic population. Those for whom no etiology is readily apparent are said to have primary or idiopathic male osteoporosis. In these individuals, histomorphometric studies indicate that this is a disorder that is more typically characterized by low turnover. Although antiresorptive agents such as alendronate have been shown to increase bone mass in men, the rationale for an anabolic agent that can stimulate bone formation is clear. The most attractive anabolic agent at this time is parathyroid hormone (PTH) administered in low dosage and intermittently. Such regimens in experimental animals have been associated with marked gains in bone mass. Slovik et al. showed that parathyroid hormone can increase vertebral bone mass in men with idiopathic osteoporosis. We have conducted the first controlled, randomized, double-blind study of PTH in men with idiopathic osteoporosis. Twenty-three men, 30-68 years old (50 +/- 1.9) with Z-scores less than -2.0 were assigned to a placebo (n = 13) or treatment (n = 10) arm. After 18 months, those who received PTH showed a 13.5 +/- 3% increase in bone mass, significantly greater than the placebo group whose bone density did not change. Femoral neck bone density increased significantly by 2.9 +/- 1.5%. The distal radius site did not change. During an open label extension for an additional 12 months, there was no further increase in bone density in the lumbar spine but the femoral neck continued to show gains. Markers of bone formation and resorption increased in the PTH arm reaching a peak between 9 and 12 months of therapy and declining thereafter. Parathyroid hormone was well tolerated. These results suggest that low-dose intermittent PTH may be an efficacious therapy for men with idiopathic osteoporosis.

Adult↗
PubMed2001

Fragment-specific actions of parathyroid hormone in isolated perfused rat hearts.

Different regions within the parathyroid hormone (PTH) molecule are known to have different biological activities. In the heart, the physiological actions of the intact PTH molecule are known as positive chronotropy and coronary vasodilatation. However, it is unclear which region of the PTH exerts which physiological action in the heart. Therefore, to clarify this point, we examined the hemodynamic effect of intact PTH(1-84) and selected PTH analogs, namely, PTH(1-34), PTH(2-34), [Nle8, 18Tyr34]PTH(3-34), PTH(4-34), [Tyr34]PTH(7-34), and PTH(13-34) in isolated perfused rat hearts. Both PTH(1-84) and PTH(1-34) significantly increased heart rate and decreased coronary perfusion pressure. In contrast, neither PTH(2-34) nor [Nle8,18Tyr34]PTH(3-34) increased heart rate, but they did decrease coronary perfusion pressure. Peptides further truncated at the amino terminus, PTH(4-34), [Tyr34]PTH(7-34), and PTH(13-34), had no effect on hemodynamics. Furthermore, the protein kinase A inhibitor H89, but not the protein kinase C inhibitor H7, attenuated the hemodynamic effects of PTH(1-34) or PTH(2-34), while it prevented those of [Nle8,18Tyr34]PTH(3-34). These results clearly demonstrate that the first amino acid of PTH is essential for its chronotropic property whereas the first 3 amino acids of PTH are involved in its coronary vasodilatory action. Furthermore, protein kinase A, but not protein kinase C, appears to be involved in the chronotropic and coronary vasodilatory actions of PTH.

Animals↗
PubMed2001

The role of estrogens in male skeletal development.

The developing human skeleton is known to be influenced by the presence of sex steroids. In girls, estrogens have been considered to be the dominant hormone, whereas in boys, androgens have occupied a primary physiological role in terms of bone mass accrual. Although these views are still current, recent observations made of rare defects in estrogen receptor sensitivity or estrogen synthesis have called attention to the importance of estrogens in the developing male skeleton. In these human genetic models, the affected men have demonstrated continuous linear skeletal growth, open epiphyses, lack of pubertal growth spurt, and reduced bone mass. In the example of men with aromatase deficiency, lacking estrogens from birth, administration of estrogen led to impressive increases in bone density, maturation of the skeletal growth plates, and cessation of linear growth. Animal models mimicking these human syndromes by knockout technology, have tended to support these observations. The data argue for a primary role of estrogens in the developing male skeleton, while not diminishing the important role for androgens.

Animals↗
PubMed2001

Signaling pathway and chronotropic action of parathyroid hormone in isolated perfused rat heart.

Parathyroid hormone (PTH) activates both adenylyl cyclase and phospholipase C via the PTH-1 receptor. We previously reported that PTH increased heart rate and that this effect was mediated via the pacemaker current (I f ). However, it has been reported that PTH exerts its chronotropic effect via an interaction with adrenergic receptors or via L-type calcium channels. Thus, the objective of the study was to elucidate the exact mechanism of the chronotropic effect of PTH. We tested whether its chronotropic effects could be abolished by inhibitors of the following systems in isolated perfused rat hearts: alpha-adrenergic (prazosin); beta-adrenergic (propranolol); angiotensin II (CV11974); endothelin-1 (TAK044); calcium channel (verapamil); adenylyl cyclase (miconazole); phospholipase C (U73122) or I f (CsCl). In addition, we measured the cyclic adenosine monophosphate level of the heart after PTH administration. Whereas prazosin, propranolol, CV11974, TAK044, verapamil, and U73122 did not inhibit the chronotropic effect of PTH, CsCl or miconazole suppressed it significantly. PTH increased the cyclic adenosine monophosphate level of the atrium but not the left ventricle. These results indicate that the chronotropic actions of PTH are mediated via selective activation of adenylyl cyclase to increase the I f current.

Adenylyl Cyclases↗
PubMed2001

Guidelines for diagnosis and therapy of MEN type 1 and type 2.

This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

Humans↗
PubMed2001

Clinical review 123: Anabolic therapy for osteoporosis.

All currently available, approved therapies for osteoporosis inhibit bone resorption. By acting at this site in the bone remodeling cycle, estrogens, selective estrogen receptor modulators, calcitonin, and the bisphosphonates all have the capacity to increase bone mineral density and to reduce the risk of new fractures. There can be no doubt that these agents have had an enormous impact on our diagnostic and therapeutic approach to osteoporosis. Despite their great value, the antiresorptives are generally not associated with dramatic increases in bone mass, and their action to reduce fracture risk, although highly significant, is rarely more than 50% of the baseline risk. Another approach is anabolic therapy, in which bone formation is directly stimulated. In this review we will summarize the anabolic agents that have been studied and present a current view of their current standing. Fluoride, GH, insulin-like growth factor I, the statins, and PTH will be reviewed. Although still in development, approaches to combination therapy with antiresorptives and anabolic agents are also promising.

Drug Therapy, Combination↗
PubMed2000

Primary hyperparathyroidism. When to observe and when to operate.

The decision to recommend parathyroid surgery in patients with symptomatic primary hyperparathyroidism is clear. The decision to recommend parathyroid surgery in patients with asymptomatic primary hyperparathyroidism is clearer than it was 10 years ago. In addition to the NIH guidelines, the author believes that patients who have vertebral osteopenia, patients who have vitamin D deficiency, and patients who are in their perimenopausal years should undergo surgery. Although surgery may be an acceptable option even for patients who do not meet these guidelines, many patients can be safely managed without surgery. For these patients, monitoring is essential because a small number will show progression of disease over time.

Female↗
PubMed2000

Tachycardia-induced cardiomyopathy secondary to thyrotoxicosis: a young man with previously unrecognized Graves' disease.

A young man with previously unrecognized Graves' disease presented with atrial fibrillation and severe low-output heart failure due to dilated cardiomyopathy. The patient's cardiomyopathy resolved and cardiac function recovered shortly after hyperthyroidism and tachycardia were treated during hospitalization. The temporal relationship between heart rate and cardiac function during the recovery period suggests that chronic tachycardia may have been an important cause of his cardiac dysfunction. Thyrotoxicosis seemed to be directly responsible for the development of sustained supraventricular tachycardia in this patient, which then led to tachycardia-induced cardiomyopathy causing severe low-output heart failure. Although relatively infrequent, this etiology should not be overlooked in patients thyrotoxicosis and heart failure. This is the first case in which the time course and the temporal relationship between the control of heart rate and the recovery of cardiac function are illustrated in a thyrotoxic patient.

Adult↗
PubMed2000

Osteoporosis: an unusual presentation of childhood Crohn's disease.

Osteoporosis is known to be associated with Crohn's disease. We report a 12-yr-old boy without a history of steroid use, in whom severe osteoporosis and multiple collapsed vertebrae were the presenting manifestations of Crohn's disease. After treatment of the Crohn's disease, he resumed normal growth and progressed through puberty. Concomitantly, he demonstrated a substantial recovery of vertebral bone mineral density and structure. Possible pathophysiological mechanisms underlying the osteoporosis and the subsequent improvement in bone density are discussed.

Alkaline Phosphatase↗
PubMed2000

Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers.

Osteoporosis in men poses a unique therapeutic challenge. Clinical studies have focused largely on the more prevalent problem of post-menopausal osteoporosis, with few gender-specific studies exploring treatment options in men. Idiopathic osteoporosis in middle-aged men presents an additional dilemma, because in the majority of patients it is a low bone turnover state for which there are currently no available anabolic agents. We conducted an 18-month randomized, double blind, placebo-controlled trial of 23 men with idiopathic osteoporosis, 30-68 yr old (mean age +/- SEM, 50 +/- 1.9 yr). All patients received 1,500 mg calcium and 400 IU vitamin D daily. Ten patients were randomized to receive 400 IU PTH-(1-34), and 13 patients received vehicle, administered by daily sc injection. Serum and urinary biochemistries, including markers of bone turnover were measured every 3 months. Bone densitometry of the lumbar spine, hip, and radius was performed every 6 months. PTH-(1-34) was associated with a marked 13.5% increase in bone mass at the lumbar spine, whereas that in the control group did not change (P < 0.001). The mean lumbar spine T-score improved from -3.5 +/- 0.2 to 2.4 +/- 0.4. Femoral neck bone mineral density in the PTH-treated group increased 2.9% (P < 0.05). The 1/3 site of the distal radius showed no change from baseline in the PTH-treated group. There were no significant changes in serum calcium concentration, 24-h urinary calcium excretion, or 1,25-dihydroxyvitamin D in either group. All markers of bone turnover increased in the PTH-treated patients, with the greatest changes in serum osteocalcin and urinary N-telopeptide (230% and 375% above baseline by 12 months, respectively; P < 0.001). Free pyridinoline and markers of bone formation that showed little correlation with each other at baseline, became highly correlated in the PTH-treated group (r = 0.1; P = 0.29 at baseline; to r = 0.7; P < 0.0001 at 18 months), a pattern absent in the control patients. The best predictor of the lumbar spine response to PTH at 18 months was the combination of pyridinoline at baseline and osteocalcin at 3 months (70% of the variance). PTH is a potent stimulator of skeletal dynamics in men with idiopathic, low turnover osteoporosis; is associated with substantial increases in lumbar spine and hip bone density; and may prove to be an efficacious anabolic agent in men with this disorder.

Adult↗