Federico Hawkins

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: A randomized, double-blind, placebo-controlled extension trial

OBJECTIVE To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus.

OBJECTIVE The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA(1c)), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia. METHODS Patients with type 2 diabetes mellitus (HbA(1c) >/=6.5% and </=9.8%) who had not previously received insulin or oral antihyperglycemic medications (OAMs) were randomized to treatment with placebo, pioglitazone 30 mg QD, or pioglitazone 45 mg QD in double-blind fashion for 16 weeks at 41 centers in Canada and Spain. RESULTS A total of 297 patients were randomized (99 in each group). Overall, 286 (96.3%) were white. Mean (SD) age was 58.4 (10.9) years (range, 24-85 years), mean (SD) body mass index was 31.4 (4.8) kg/m(2), mean (SD) duration of type 2 diabetes mellitus was 20.0 (37.4) months, and 30.6% of patients were receiving medication for dyslipidemia. Treatment with pioglitazone 30 or 45 mg QD for 16 weeks reduced mean HbA(1c) by 0.8% and 0.9% from baseline, respectively (both P < 0.001 vs baseline and placebo). A reduction in HbA(1c) of 0.2% was observed in the placebo group (P = 0.025). In patients with medium (>/=7% to <8%) or high (>/=8% to </=9.8%) baseline HbA(1c), both doses of pioglitazone significantly reduced HbA(1c) (both P < 0.001 vs placebo). Pioglitazone 30 and 45 mg significantly reduced fasting serum insulin versus placebo (P = 0.008 and P = 0.006, respectively) and increased insulin sensitivity by Homeostasis Model Assessment versus placebo (P = 0.039 and P = 0.001, respectively). Relative to placebo, pioglitazone 30 and 45 mg significantly increased high-density lipoprotein cholesterol (HDL-C [P = 0.028 and P < 0.001, respectively]) and lowered the atherogenic index of plasma (P = 0.018 and P < 0.001, respectively). Pioglitazone 45 mg also significantly reduced serum triglycerides, apolipoprotein B, and total cholesterol:HDL-C ratio versus placebo (P = 0.007, P = 0.015, and P = 0.005, respectively). Pioglitazone 30 and 45 mg were associated with a significant reduction in serum alanine aminotransferase relative to placebo (P = 0.036 and P = 0.005, respectively). Pioglitazone appeared to be safe and was well tolerated. CONCLUSIONS In the present study, pioglitazone 30 and 45 mg produced significant improvements in HbA(1c), insulin sensitivity, and lipid profile in OAM-naive patients with type 2 diabetes mellitus with suboptimal glycemic control and mild dyslipidemia.

CALCITONIN AND BISPHOSPHONATES TREATMENT IN BONE LOSS AFTER LIVER TRANSPLANTATION

Osteopenia is a major complication of orthotopic liver transplantation (OLT). However, no effective therapy for bone disease has been defined. We have studied vertebral bone mineral density (VMD) and fasting serum markers of bone formation [bone gla protein (BGP), procollagen I carboxyterminal peptide (PICP)] and metabolism (serum Ca, P, intact parathyroid hormone (iPTH), 25OHD3 and 1,25(OH)2D3) in 120 patents after OLT. VMD was measured by dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000 densitometer on two occasions, 12 months apart. Patients with OLT had a VBD significantly lower compared with age- and sexed-matched Spanish controls (P<0.05). Prevalence of osteoporosis (Z score below-2 SD) was 35.8%. Serum BGP (8.6±0.7 ng/ml) and PICP (222.9±81.9 ng/dl) were higher than those of controls. However, serum calcium, phosphorus, iPTH, 25OHD3, and 1,25(OH)2D3 were within normal range. Patients with osteoporosis were randomly treated with 40 IU/day of calcitonin i.m. (Diatin, Ferrer Int. Laboratories) (n=17) or 400 mg p.o., 15 days every 3 months, of sodium ethiodronate (Difosfen, Rubio Laboratories) (n=23). All patients received 500 mg/12 hours of elemental calcium p.o. After 12 months of treatment, a significant increment of vertebral mineral density (VMD) was observed (6.4% and 8.2%, respectively). Serum BGP and PICP values remained elevated without a difference between the two drugs. Our results indicate that antiresorptive drugs may be of benefit in the high turnover osteoporosis of OLT recipients.

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults

objective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.

Comparative Effects of Teriparatide and Strontium Ranelate on Bone Biopsies and Biochemical Markers of Bone Turnover in Postmenopausal Women With Osteoporosis

We assessed the effects on bone remodeling and histomorphometry after daily subcutaneous injections of teriparatide (n = 39, 20 μg/d) or oral strontium ranelate (SrR, n = 40, 2 g/d) in postmenopausal women with osteoporosis. Evaluable biopsies were obtained from 29 patients in the teriparatide group and 22 in the SrR group after 6 mo of treatment. The mean ± SD mineralization surfaces as a percent of bone surfaces (MS/BS, %) at the trabecular level were 7.73 ± 1.48% for teriparatide and 5.25 ± 1.15% for SrR (p = 0.219) and at the endocortical level were 17.22 ± 3.06% and 9.70 ± 2.07%, respectively (p = 0.052). Cortical porosity was 5.40 ± 0.41% in the teriparatide and 4.14 ± 0.40% in the SrR group (p = 0.037). Teriparatide induced significant increases from baseline in bone formation and resorption markers, reaching statistical significance for amino‐terminal propeptide of type I collagen (PINP) after 1 mo (+57%, p < 0.001). SrR induced small, but statistically significant, reductions from baseline in PINP at 3 (−14%, p = 0.005) and 6 mo (−19%, p < 0.001) and in serum β‐C‐terminal telopeptide of type I collagen (β‐CTX) at 1 and 3 mo (−11%, for both, p < 0.05). There were more patients with adverse events after SrR (70%) than teriparatide (41%) treatment (p = 0.013). In conclusion, the changes in biochemical markers of bone formation confirmed bone‐forming activity of teriparatide but not of SrR treatment. The effects of SrR on bone remodeling and cell activity were modest, indicating that its effects on fracture reduction may be predominantly mediated through a different mechanism than that observed with anabolic or more potent antiresorptive agents.

Fine needle aspiration biopsy in the diagnosis of thyroid cancer and thyroid disease

Fine needle aspiration biopsy (FNAB) performed for diffuse and nodular goiter in the past 5 years, was evaluated in 1399 cases. Surgery was performed on the basis of FNAB cytologic diagnosis that was positive or suggestive of malignancy and/or a suggestive clinical history. Surgery also was performed in cases of cold nodules with negative FNAB results that did not respond to 6 months of suppressive thyroxine therapy. A correlation of cytologic findings with histologic findings was possible in 415 patients who underwent surgery: the evaluation of FNAB results yielded better results when suspicious cytologic findings were considered to be positive (2.4% false‐negative, 86.3% sensitivity) rather than negative (6.5% and 65.7%, respectively). FNAB has become a useful procedure in the study and diagnosis of thyroid diseases. It is a simple, rapid diagnostic procedure that may be used to expedite the management ofmalignant lesions. Cancer 59:1206‐1209, 1987.

Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs trial.

Data on treatment of glucocorticoid‐induced osteoporosis (GIO) in men are scarce. We performed a randomized, open‐label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T‐score ≤ –1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1–L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high‐resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X‐ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18‐month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE‐derived strength than risedronate.

Quantitative Ultrasound Calcaneus Measurements: Normative Data and Precision in the Spanish Population

Abstract:Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. In this study we have determined the normative QUS data in the Spanish population for the Sahara Clinical Sonometer (Hologic). Broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were determined. We also studied the precision in vivo and in vitro. The short-term in vivo precision (CV) was 4.88% for BUA, 0.36% for SOS, 3.45% for QUI and 4.15% for BMD, while in vitro precision was 0.40% for SOS and 2.67% for BUA. Our results are comparable to reference population data previously published in other countries and may serve as reference normative data for both genders in Spain.

Bone Mineral Density in Children and Adolescents with Diabetes Mellitus Type 1 of Recent Onset

Abstract. There is still controversy over the impact of diabetes control and duration on bone mass and growth parameters in children and adolescents with insulin-dependent diabetes mellitus (IDDM). The aim of this study was to assess bone mineral density (BMD) at axial and appendicular sites, in children with noncomplicated IDDM of recent onset, and its relation to metabolic control and auxological parameters (weight, height, and puberal stage). Fifty-five young Spanish IDDM, otherwise healthy patients (26 males, aged (SD 9.7 ± 4.3 years) and 29 females, aged (SD 11.2 ± 3.8 years) were studied. Duration of diabetes was 1–13.8 years. Two hundred eighty-two age-matched, healthy, Spanish children served as controls. HbA1 was assayed by high pressure liquid chromatography (HPLC) and BMD was measured using dual X-ray absorptiometry (DXA) densitometry at the spine and forearm. Results showed a Gaussian BMD distribution of patients according to sex and age, without sexual-stage differences. There was no correlation between BMD and glycated hemoglobin (average life disease or last HbA1 values) or duration of the disease; moreover, no differences in bone mass were found between <3 and ≥3 years of disease duration. Diabetes impact index (mean HbA1× duration of disease in months) showed no significant influence of diabetes control on BMD. We could not demonstrate any impact of diabetes on BMD and growth parameters in children with IDDM of short duration.

Bone density and turnover in Addison's disease: effect of glucocorticoid treatment

Osteoporosis is a well-known side-effect of chronic treatment with glucocorticoids. We have studied vertebral bone mineral density (BMD) and biochemical markers of bone metabolism in 30 patients diagnosed of Addisons disease (AD) to determine the effect of long-term replacement treatment with hydrocortisone (30 mg/day) or prednisone (7.5 mg/day). Lumbar bone mineral density was measured with dual energy X-ray absorptiometry in L-1-4 in two occasions, separated by 12 months. BMD in premenopausal women and men with AD was similar to healthy controls and postmenopausal women had slightly lower results. Rate of change of bone density followed up over a period of 12 months was -0.82%. Bone loss was not influenced by duration or type of steroid treatment. Biochemical parameters, serum calcium, alkaline phosphatase, osteocalcin, procollagen type I, PTH and 25(OH)vitamin D were within normal limits. Our results show that in patients with AD, after replacement with low doses of glucocorticoids there is no significative trabecular bone loss neither modifications in bone formation markers.