Risk Factors for Low Bone Density in Inflammatory Bowel Disease: Use of Glucocorticoids, Low Body Mass Index, and Smoking.

BACKGROUND: Inflammatory bowel disease (IBD) patients are reported to have lower bone density compared to healthy controls. There is limited consensus regarding factors affecting bone density among these patients. Our aim, therefore, was to determine clinical and genetic variables that contribute to lower bone mineral density (BMD) in IBD patients. METHODS: A cross-sectional study of IBD patients treated in a tertiary referral center was performed. Epidemiological and clinical data were collected, and genetic testing for the common mutations in Nucleotide-binding Oligomerization Domain-containing protein (NOD)2 was performed. We examined correlations between the different variables and BMD in the total hip, femoral neck, and lumbar spine. RESULTS: Eighty-nine patients (49% males, 67 Crohn's disease [CD]) participated in the study. 42Forty-two (63%) of the CD and 13 (59%) of the ulcerative colitis patients met the criteria for osteoporosis/osteopenia. Factors associated with lower Z scores were low body mass index (BMI; r = -0.307, p = 0.005), use of glucocorticoids (likelihood ratio [LR] 5.1, p = 0.028), and a trend for male gender (LR = 3.4, p = 0.079). Among CD patients, low bone density showed borderline significance for association with gastrointestinal surgery (LR = 4.1, p = 0.07) and smoking (LR = 3.58, p = 0.06). Low levels of 25OHD were not associated with low BMD, nor were mutations in NOD2. No increased rate of fractures was seen among patients with osteopenia or osteoporosis. CONCLUSION: In addition to the generally accepted risk factors for osteoporosis (glucocorticoids, low BMI, smoking), male IBD patients had a trend toward lower BMD. Carrying a mutaticon in NOD2 did not confer a risk for bone loss.

Cost and Consequences of Nonadherence With Oral Bisphosphonate Therapy: Findings From a Real-World Data Analysis.

BACKGROUND: Adherence to osteoporosis treatment remains poor despite available treatments and physician and patient education. This study aims to determine the effect of low adherence in real-world data. OBJECTIVE: To examine the association between adherence with oral bisphosphonate therapy and fracture risk as well as health care resource utilization. METHODS: Women included in this retrospective analysis were 55 years or older and had started oral bisphosphonate therapy between 2005 and 2011 in a large not-for-profit health care center in Israel. Adherence to therapy was measured by the medication possession ratio (MPR) during the first year from therapy initiation. Patients with MPR lower than 70% were considered nonadherent. Study outcomes were osteoporotic fracture events and health care utilization (including physician visits and hospitalizations) during the second year from therapy initiation. RESULTS: Among the 17 770 women included in the analysis (mean age = 66.5 years; SD = ±8.3 years), 48.9% were nonadherent to therapy during the first year of treatment. Osteoporotic fracture risks during the second year among adherent and nonadherent patients were 2.1% and 2.5%, respectively (P = 0.1). When analysis was limited to patients 75 years or older, nonadherence with bisphosphonates was associated with an adjusted odds ratio of 1.49 (95% CI = 1.08-2.04) for osteoporotic fractures compared with adherent patients. Nonadherent patients had 13.4% higher medical costs than their adherent counterparts among patients 75 years and older (P = 0.002). CONCLUSIONS: In patients 75 years and older, nonadherence with oral bisphosphonates can be associated with significantly greater short-term risk of osteoporotic fractures and higher utilization of health care services.

Safety and Efficacy of Oral Human Parathyroid Hormone (1-34) in Hypoparathyroidism: An Open-Label Study.

The standard treatment of primary hypoparathyroidism (hypoPT) with oral calcium supplementation and calcitriol (or an analog), intended to control hypocalcemia and hyperphosphatemia and avoid hypercalciuria, remains challenging for both patients and clinicians. In 2015, human parathyroid hormone (hPTH) (1-84) administered as a daily subcutaneous injection was approved as an adjunctive treatment in patients who cannot be well controlled on the standard treatments alone. This open-label study aimed to assess the safety and efficacy of an oral hPTH(1-34) formulation as an adjunct to standard treatment in adult subjects with hypoparathyroidism. Oral hPTH(1-34) tablets (0.75 mg human hPTH(1-34) acetate) were administered four times daily for 16 consecutive weeks, and changes in calcium supplementation and alfacalcidol use, albumin-adjusted serum calcium (ACa), serum phosphate, urinary calcium excretion, and quality of life throughout the study were monitored. Of the 19 enrolled subjects, 15 completed the trial per protocol. A median 42% reduction from baseline in exogenous calcium dose was recorded (p = .001), whereas median serum ACa levels remained above the lower target ACa levels for hypoPT patients (>7.5 mg/dL) throughout the study. Median serum phosphate levels rapidly decreased (23%, p = .0003) 2 hours after the first dose and were maintained within the normal range for the duration of the study. A notable, but not statistically significant, median decrease (21%, p = .07) in 24-hour urine calcium excretion was observed between the first and last treatment days. Only four possible drug-related, non-serious adverse events were reported over the 16-week study, all by the same patient. A small but statistically significant increase from baseline quality of life (5%, p = .03) was reported by the end of the treatment period. Oral hPTH(1-34) treatment was generally safe and well tolerated and allowed for a reduction in exogenous calcium supplementation, while maintaining normocalcemia in adult patients with hypoparathyroidism. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

[Minimally invasive parathyroidectomy for treatment of primary hyperparathyroidism caused by parathyroid adenoma].

BACKGROUND: Minimally invasive parathyroidectomy (MIP) is frequently used for the treatment of primary hyperparathyroidism (PHPT) caused by a single adenoma. This method depends on preoperative localization of the tumor by a sestamibi scan, cervical ultrasound, and intraoperative parathyroid hormone (PTH) measurements. When the sestamibi scan is negative, the classical 4-gland exploration is used instead of MIP. AIMS: a. To evaluate the effectiveness of MIP for treatment of PHPT caused by adenoma. b. To evaluate the use of PTH selective venous sampling (PTH-SVS) in patients with negative sestamibi scintigraphy. METHODS: MIP was performed in all patients in whom an adenoma was diagnosed by sestamibi scan and US. When the sestamibi scan was negative, PTH-SVS was performed preoperatively for localization of the adenoma. RESULTS: Parathyroidectomy was performed in 541 patients, 458 with PHPT and 83 with secondary hyperparathyroidism. In 345 of 380 patients (90.8%) with an adenoma, MIP was performed, and in 92 of these patients the operation was performed under local anesthesia. A total of 444 (97.0%) of the patients with PHPT were cured by the surgery. In 56 patients with a negative sestamibi scan, PTH-SVS was used preoperatively for localization of an adenoma. In 30 of these cases (53%) MIP was successfully performed in spite of a negative sestamibi scan. CONCLUSIONS: MIP is the treatment of choice for PHPT caused by a single adenoma. When the preoperative sestamibi scan is negative, the authors recommend the use of PTH-SVS for preoperative localization. This resulted in 53% successful MIP in patients with a negative sestamibi scan.

Epidemiology and correlates of osteoporotic fractures among type 2 diabetic patients.

This study analyzed data on 87,224 osteoporotic patients with up to 18 years of computerized medical history. Patients with osteoporosis and type 2 diabetes had higher bone density yet more fractures than non-diabetic osteoporotic patients. Fracture incidence among the diabetic patients was associated with retinopathy and cardiovascular disease, but not with diabetes duration. PURPOSE: Little is known about the association between type 2 diabetes mellitus (T2DM) and fragility fractures or the mechanism(s) involved. We examined fracture correlates among T2DM patients with osteoporosis. METHODS: We used electronic health records of an osteoporosis (OP) registry cross-linked with a diabetes registry of a large payer provider healthcare organization in Israel. A cross-sectional analysis compared osteoporosis patients with and without T2DM, and a longitudinal Cox proportional hazard regression was used to identify incident fracture correlates. RESULTS: As of December 2015 a total of 87,224 current OP patients were identified, of whom 15,700 (18%) had T2DM. The T2DM OP patients were characterized by older age (mean 74.6 vs. 69.5), more males (20.3 vs. 14.0%), and a higher rate of chronic comorbidities compared to OP without diabetes. All major OP fractures (hip, spine, humerus, and forearm) were significantly more prevalent among T2DM OP patients (44 vs. 32%), with an overall age-standardized ratio of 1.22 (95% CI 1.19 to 1.25) and 1.15 (95% CI 1.10 to 1.21) for females and males respectively. The average T-scores were higher (femur neck - 1.8 vs. - 1.9, total hip - 1.2 vs. - 1.6, and vertebrae - 1.3 vs. - 1.7) for the T2DM OP patients compared to the non-T2DM OP patients. Among women with coexisting T2DM and osteoporosis (n = 10,812), fracture incidence was significantly associated with retinopathy (HR = 1.24, 95% CI 1.05 to 1.47) and cardiovascular disease (HR = 1.22, 95% CI 1.10 to 1.36) after controlling for age, bone mineral density T-score, rheumatoid arthritis, glucocorticoids, alcohol, and smoking). CONCLUSION: This large population-based study confirms the higher fracture risk of osteoporotic patients with T2DM, as compared to osteoporotic patients without T2DM, despite higher bone mineral density levels. The presence of micro- and macrovascular disease appears to increase this risk.

Paget's disease of bone or osteopetrosis?

We report a previously undescribed case of diffuse, scan-negative, and low active form of bone disease carrying clinical, x-ray, and biochemistry signs of Paget's disease of bone, which is analyzed in comparison with different forms of osteopetrosis.

Managing Osteoporosis: A Survey of Knowledge, Attitudes and Practices among Primary Care Physicians in Israel.

BACKGROUND: Osteoporosis is a systemic skeletal disorder characterized by impaired bone quality and microstructural deterioration leading to an increased propensity to fractures. This is a major health problem for older adults, which comprise an increasingly greater proportion of the general population. Due to a large number of patients and the insufficient availability of specialists in Israel and worldwide, osteoporosis is treated in large part by primary care physicians. We assessed the knowledge of primary care physicians on the diagnosis and treatment of osteoporosis. METHODS: Physician's knowledge, sources of knowledge acquisition and self-evaluation of knowledge were assessed using a multiple choice questionnaire. Professional and demographic characteristics were assessed as well. RESULTS: Of 490 physicians attending a conference, 363 filled the questionnaires (74% response rate). The physicians demonstrated better expertise in diagnosis than in medications (mechanism of action, side effects or contra-indications) but less than for other treatment related decisions. Overall, 50% demonstrated adequate knowledge of calcium and vitamin D supplementation, 51% were aware of the main therapeutic purpose of osteoporosis pharmacotherapy and 3% were aware that bisphosphonates should be avoided in patients with impaired renal function. Respondents stated frontal lectures at meetings as their main source of information on the subject. CONCLUSION: The study indicates the need to intensify efforts to improve the knowledge of primary care physicians regarding osteoporosis, in general; and osteoporosis pharmacotherapy, in particular.

Vitamin D Status and Quality of Life in Healthy Male High-Tech Employees.

While low vitamin D status has been shown to be associated with decreased quality of life in unhealthy populations and women, only limited data are available regarding healthy adult men. Our aim was to evaluate the associations between health-related quality of life (QoL) and vitamin D status in adult men. High-tech employees aged 25-65 year were recruited from an occupational periodic examination clinic at Rambam Health Campus. QoL was assessed using the Centers for Disease Control and Prevention (CDC) Health-related quality of life questionnaire (HRQOL-4). Serum 25-hydroxyvitamin D (25(OH)D) and Body Mass Index (BMI) were measured; further information was collected about physical activity, education, sun exposure, sick-days, and musculoskeletal pain severity (visual analog scale). Three hundred and fifty-eight men were enrolled in the study; mean serum 25(OH)D level was 22.1 ± 7.9 ng/mL (range 4.6-54.5 ng/mL). In a multivariate logistic regression model, 25(OH)D was a significant independent determinant of self-rated health; Odds Ratio (OR) for self-rated health was 0.91 (95% confidence interval (CI) 0.85-0.97, p = 0.004), adjusted for age, BMI, pain severity, physical activity, and sun exposure. Every 1 ng/mL increase of 25(OH)D was associated with 9% reduction in the odds of reporting self-rated health as fair or poor. Poisson regression model demonstrated an association between physically unhealthy days and 25(OH)D levels (rate ratio 0.95, p < 0.001). In conclusion, serum levels of 25(OH)D were associated with self-rated health and with physically unhealthy days of HRQOL in healthy high-tech male workers. Future intervention studies are required to test the impact of vitamin D supplementation on QoL.

Minimally invasive surgery for treatment of hyperparathyroidism.

BACKGROUND: Minimal invasive surgery for parathyroidectomy has been introduced in the treatment of hyperparathyroidism. OBJECTIVE: To evaluate the contribution of the sestamibi-SPECT (MIBI) localization, cervical ultrasonography, and intraoperative rapid turbo intact parathormone assay in minimal invasive parathyroidectomy. METHODS: Between August 1999 and March 2004, 146 consecutive hyperthyroid patients were treated using the MIBI and ultrasound for preoperative localization and iPTH measurements for intraoperative assessment. RESULTS: Parathyroid adenoma was detected in 106 patients, primary hyperplasia in 16, secondary hyperplasia in 16, tertiary hyperplasia in 5, and parathyroid carcinoma in 1 patient. Minimal invasive exploration of the neck was performed in 84 of the 106 patients (79.2%) with an adenoma, and in 17 of them this procedure was performed under local cervical block anesthesia in awake patients. Adenoma was correctly diagnosed by MIBI scan in 74% of the patients, and by ultrasound in 61%. The addition of ultrasonography to MIBI increased the accuracy of adenoma detection to 83%. In 2 of the 146 patients (1.4%) iPTH could not be significantly reduced during the initial surgical procedure. Minimal invasive surgery with minimal morbidity, and avoiding bilateral neck exploration, was achieved in 79.2% of patients with a primary solitary adenoma. CONCLUSIONS: Preoperative localizationof the parathyroid gland by MIBI and ultrasound together with intraoperative iPTH measurements resulted in an overall cure rate of 98.6% for the entire series, The addition of ultrasound to the MIBI scan increased the accuracy of adenoma detection.

Calcium supplementation provides an extended window of opportunity for bone mass accretion after menarche.

BACKGROUND: High calcium intakes during adolescence may increase bone acquisition. The magnitude of the effect of dietary calcium supplementation and the timing of its administration to achieve significant effects on bone health are still incompletely defined. OBJECTIVE: The objective of this study was to assess the effect of calcium supplementation on bone mass accretion in postmenarcheal adolescent girls with low calcium intakes. DESIGN: A double-blind, placebo-controlled calcium supplementation study was implemented. One hundred girls with a mean (+/- SD) age of 14 +/- 0.5 y with habitual calcium intakes < 800 mg/d completed a 12-mo protocol. The treatment group received a daily supplement containing 1000 mg elemental calcium. Bone mineral density (BMD) and bone mineral content (BMC) of the total body, lumbar spine, and femoral neck were determined at inclusion, 6 mo, and 12 mo. Also measured were serum concentrations of biochemical markers of bone turnover (osteocalcin and deoxypyridinoline), parathyroid hormone, and vitamin D. RESULTS: The calcium-supplemented group had greater accretion of total-body BMD and lumbar spine BMD but not BMC than did the control group. Calcium supplementation appeared selectively beneficial for girls who were 2 y postmenarcheal. Calcium supplementation significantly decreased bone turnover and decreased serum parathyroid hormone concentrations. CONCLUSION: Calcium supplementation of postmenarcheal girls with low calcium intakes enhances bone mineral acquisition, especially in girls > 2 y past the onset of menarche.

Monitoring response to osteoporosis therapy with alendronate by a multisite ultrasound device: a prospective study.

BACKGROUND: Osteoporotic fractures are a major health problem among postmenopausal women. A significant proportion of subjects with low bone density are currently undiagnosed. Peripheral devices can be used for osteoporosis diagnosis, but their role in long-term monitoring of skeletal changes is unclear. The current study evaluated the ability of quantitative ultrasound (QUS) measurements to follow osteoporotic subjects treated with alendronate. METHODS: QUS measurements were done with Sunlight Omnisense (Omnisense, Sunlight Medical Ltd., Tel Aviv, Israel), which determines the bone speed of sound (SOS) in several skeletal sites. Postmenopausal women with T-scores of -2 or less at one site were recruited and treated with alendronate for at least 1 yr. Follow-up was done with QUS and dual-energy X-ray absorptiometry (DXA) (Lunar DPX scanner, Madison, WI, USA) measurements. RESULTS: After 12 mo, bone mineral density (BMD) increased significantly at the lumbar spine (LS) (0.34 +/- 0.08 T-score, p = 0.0001 with 95% CI [0.19, 0.49]) and QUS at the tibia (TIB) (0.21 +/- 0.09 T-score, p = 0.02 with 95% CI [0.03, 0.39]). After 12 mo, a significant increase in mean T-scores was demonstrated in all sites assessed according to baseline T-score of -2 or less. CONCLUSIONS: Peripheral QUS measurement may be considered for follow-up on skeletal changes in response to alendronate treatment.

Predictors of serum 25(Oh)D increase following bimonthly supplementation with 100,000IU vitamin D in healthy, men aged 25-65 years.

UNLABELLED: Vitamin D replenishment therapy typically entails standard dosages, but related increases in serum 25(OH)D levels vary between individuals. This study was aimed to identify factors that affect the efficacy of vitamin D supplementation. SUBJECTS AND METHODS: 79 healthy men aged 25-65 with 25(OH)D<20ng/ml participated in a vitamin D supplementation study. All participants received 100,000IU vitamin D bimonthly, e.g., 1666IU/day. Personal and demographic information, physical activity and sun-exposure questionnaires were completed by the participants. Weight, height, and waist circumference were recorded. Serum calcium, creatinine, 25(OH)D, PTH, lipid profile, and liver-enzyme levels were assessed. All measurements were repeated after 6 and 12 months. The difference between baseline serum 25(OH)D and 12-month measurements was calculated (delta). Linear regression was performed to identify predictors for increases in 25(OH)D levels. RESULTS: Mean serum 25(OH)D level increases according to BMI were 12.6±5.29ng/ml for BMI≤25, 10.12±4.95ng/ml for 2530, which differed significantly from the other BMI categories (p=0.003). In a regression model to predict 25(OH)D increase, BMI was the main predictor (p<0.001), explaining 21.6% of the variance in serum 25(OH)D (inverse association). Age, sun-exposure, serum cholesterol, physical-activity, baseline 25(OH)D levels and seasonality were insignificant. The full model explained 27.9% of the variance in serum 25(OH)D. CONCLUSION: This study's main findings are that BMI affect vitamin D response in healthy men. Quantitative supplementation adjustments may be warranted in obese men, for whom the dose may need to be doubled. This article is part of a special issue entitled '16th Vitamin D Workshop'.

Physical activity and bone mineral density in adolescents with vitamin D deficiency.

INTRODUCTION: Studies have shown that physical activity (PA) is superior to many other environmental factors in determining bone mineral density (BMD), but none has examined the independent relationship between PA and vitamin D status. PURPOSE: The aim of this study was to assess the relationship among amount of PA, vitamin D (25(OH)D), and BMD. METHODS: A total of 166 female ballet dancers and sedentary adolescents were divided by tertiles of serum levels of 25(OH)D (< 11.3, 11.3-14.9, and > or = 15 ng·mL(-1)). Diet, PA, and menstruation were assessed by questionnaires; BMD was measured in three sites by dual-energy x-ray absorptiometry. RESULTS: Across 25(OH)D tertiles, there were no differences in mean participant age, weight, height, PA, calcium and energy intake, BMD, or parathyroid hormone. PA was positively associated with BMD in participants with vitamin D deficiency. Multivariable regression analysis, controlling for age, body mass index, parathyroid hormone, and bone turnover markers, showed that total body, femoral neck, and lumbar spine BMD were all positively related to PA, with regression coefficients increasing as vitamin D levels dropped across tertiles. CONCLUSIONS: PA is positively related to BMD in vitamin D-deficient female adolescents and with increasing magnitude as serum vitamin D levels drop. These findings suggest that PA may counteract the detrimental effect of marked vitamin D deficiency on bone mass.

Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice.

BACKGROUND: There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations. METHODS: Twenty-five experts from various disciplines (classical clinical applications, cardiology, autoimmunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale. RESULTS AND CONCLUSION: Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care. A target range of at least 30 to 40 ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3 months of supplementation. An assay measuring both 25(OH)D(2) and 25(OH)D(3) is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing.

Alveolar bone loss in liver transplantation patients: relationship with prolonged steroid treatment and parathyroid hormone levels.

AIM: To evaluate the relationship among alveolar bone loss (ABL), bone status and calcium-regulating hormones in liver transplantees. PATIENTS AND METHODS: Twenty-one liver transplantees underwent a full oral examination. The correlations among bone densitometry, bone metabolic status and drug treatment were examined. RESULTS: Twelve patients had osteopenia, and six were osteoporotic. ABL was 4.33+/-2.32 mm (range 0.67-9.92). Parathyroid hormone (PTH) levels ranged from 14 to 106 (mean 55.2+/-26.4). The mean 25(OH)D(3) was 11.68+/-4.7, range 3.5-21.1 ng/ml. Nine patients were vitamin D deficient (<10 ng/ml); none of the patients had 25(OH)D(3) levels > or =30 ng/ml. No correlation was found between ABL and current or total glucocorticoids dose, although there was an inverse relation with the duration of treatment (r =-0.474, p=0.03). A positive correlation was found between ABL, PTH (r =0.419, p=0.059) and hip bone mineral density (BMD) (r=0.482, p=0.027). ABL correlated closely with age, PTH, glucocorticoid treatment (duration) and hip BMD (r =0.810, p=0.004). CONCLUSIONS: The majority of liver transplant patients had insufficient 25(OH)D(3) serum levels. Changes in calcium-regulating hormones and hip BMD were correlated with ABL. Therefore, therapeutic intervention aimed at treating vitamin D deficiency and secondary hyperparathyroidism should be considered in these patients. The benefits of vitamin D treatment in the management of secondary hyperparathyroidism and possible decrease in ABL deserve further evaluation in controlled trials.

Parathyroid hormone response to tracheal intubation in hyperparathyroid patients and normal subjects.

The stress of direct laryngoscopy and passing an endotracheal tube through the vocal cords elicits haemodynamic, metabolic and hormonal changes such as raising blood catecholamine levels. Catecholamines are known stimulants of PTH secretion. The effect of tracheal intubation on plasma parathyroid hormone levels has not yet been investigated. We monitored changes in plasma parathyroid hormone levels before and after tracheal intubation in 72 hyperparathyroid patients undergoing elective parathyroidectomy for primary and secondary hyperparathyroidism. These findings were compared to data collected from 20 subjects who underwent elective surgery (thyroidectomy or laparoscopic cholecystectomy) under general anesthesia. In the control group, tracheal intubation significantly increased plasma parathyroid hormone levels from 59 +/- 31 pg/ml to 91 +/- 40 pg/ml (mean +/- SD) (p<0.0003). In primary hyperparathyroid patients, the identical procedure increased plasma parathyroid hormone levels from 206 +/- 104 pg/ml to 217 +/- 113 pg/ml (p = 0.12) and from 898 +/- 495 pg/ml to 1162 +/- 613 pg/ml (p = 0.07) in secondary hyperparathyroidism patients. We concluded that tracheal intubation raises plasma parathyroid hormone levels. The mechanism underlying this response requires further investigation.

Rapid and sustained relief from the symptoms of carcinoid syndrome: results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide.

This 6-month, open, non-controlled, multicenter, dose-titration study evaluated the efficacy and safety of 28-day prolonged-release (PR) lanreotide in the treatment of carcinoid syndrome. Eligible patients had a carcinoid tumor with > or =3 stools/day and/or > or =1 moderate/severe flushing episodes/day. Six treatments of 28-day PR lanreotide were administered by deep subcutaneous injection. The dose for the first two injections was 90 mg. Subsequent doses could be titrated (60, 90, 120 mg) according to symptom response. Seventy-one patients were treated. Flushing decreased from a mean of 3.0 at baseline to 2.3 on day 1, and 2.0 on day 2, with a daily mean of 2.1 for the first week post-treatment (p < 0.05). Diarrhea decreased from a mean of 5.0 at baseline to 4.3 on day 1 (p < 0.05), and 4.5 on day 2, with a daily mean of 4.4 for the first week post-treatment (p < 0.001). Symptom frequency decreased further after the second and third injections, and reached a plateau after the fourth injection. By month 6, flushing and diarrhea had significantly decreased from baseline by a mean of 1.3 and 1.1 episodes/day, respectively (both p < or = 0.001); 65% of patients with flushing as the target symptom and 18% of diarrhea-target patients achieved > or =50% reduction from baseline. Median urinary 5-hydroxyindoleacetic acid and chromogranin A levels decreased by 24 and 38%, respectively. Treatment was well tolerated. 28-day PR lanreotide was effective in reducing the symptoms and biochemical markers associated with carcinoid syndrome.