Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AIs) represent the first-line adjuvant therapy for hormone receptor-positive breast cancer (BC) women. AIs have been associated with an increased rate of fractures. The aim of our study was to investigate trabecular bone score (TBS) and bone quantitative ultrasound (QUS) measurements as bone quality surrogates in AIs users. METHODS: Sixty postmenopausal BC women starting AIs and forty-two controls (mean age 61.64 ± 8.33 years) were considered. Bone mineral density (BMD) at lumbar spine and femoral neck and TBS were measured by DXA; QUS-derived Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), and Ultrasound Bone Profile Index (UBPI) were assessed at phalangeal site; morphometric vertebral fractures (Vfx) by X-ray, serum bone-specific alkaline phosphatase (BSAP), and C-telopeptide of type 1 collagen (CTX) were also evaluated. RESULTS: After 18 months, changes of TBS vs baseline were significantly different between AIs group and controls [Δ TBS - 2.2% vs - 0.4%, respectively, p = 0.001]. AD-SoS, BTT and UBPI values decreased only in AIs' group (- 3.7%, - 6.45%, -8.5%, vs baseline, respectively, pall < 0.001). 3 Vfx occurred in AIs users and were associated with the greater TBS and AD-SoS modifications. In the AIs' group, ΔTBS was associated with ΔAD-SoS (r = 0.58, p < 0.001) and ΔUBPI (r = 0.415, p = 0.001), but not with ΔBMD. Moreover, ΔTBS was independently predicted by ΔAD-SoS, after correcting for BMD, CTX and BSAP level changes (ß = 0.37, SE = 2.44, p < 0.001). CONCLUSIONS: TBS and phalangeal QUS provide useful information related to bone quality in AI-treated BC survivors and could be considered for fracture risk evaluation.

Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab.

PURPOSE: Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab. METHODS: 35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5 years) and treated with denosumab 60 mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39). RESULTS: In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = -0.39, P = 0.02; r = -0.49, P = 0.01, respectively). CONCLUSIONS: Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

Effects of teriparatide on bone mineral density and quality of life in Duchenne muscular dystrophy related osteoporosis: a case report.

Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle disease characterized by secondary osteoporosis and increased fractures. We describe the case of a 20-year-old boy with DMD suffering from back pain due to multiple vertebral fractures who was treated with teriparatide. Improvement of bone density, pain, and quality of life was achieved. DMD is an X-linked recessive muscle disease with secondary osteoporosis and related frequently occurring fractures. To date, only bisphosphonates have been used to treat osteoporosis in DMD. Black bear parathyroid hormone has been previously reported to enhance bone mass in the dystrophin-deficient mouse. This study reports the positive effect of osteoanabolic treatment with once-daily recombinant human parathyroid hormone 1-34 (rhPTH 1-34, teriparatide) in a 20-year-old DMD boy suffering from multiple vertebral fractures causing back pain. Bone formation and resorption markers (osteocalcin and C-telopeptide of type I collagen, respectively), as expected, increased within 6 months and intensity of back pain early decreased, with no pain reported after 6 months at visual analog scale. Over a 18-month period of treatment with teriparatide, bone mineral density and quality of life, assessed by the 36-item short-form questionnaire, considerably improved and no side effects were reported. Further studies on large cohorts are warranted to test the efficacy of this promising treatment for DMD related osteoporosis.

Vitamin D and bone mineral density changes in postmenopausal women treated with strontium ranelate.

OBJECTIVE: Vitamin D deficiency is widespread and often reported in subjects treated for osteoporosis. Optimal vitamin D repletion was previously shown to maximize the efficacy of anti-resorptive agents. To date, no information exists about the role of vitamin D in the response to strontium ranelate (SrR) treatment. The aim of our study was to investigate the BMD response to SrR in accordance with change of vitamin D status. METHODS: A retrospective analysis of 108 women receiving SrR for postmenopausal osteoporosis was carried out. Women were treated with SrR (2 g/day), with cholecalciferol (25,000 IU biweekly) and calcium carbonate as appropriate. Lumbar spine and femoral neck BMD, bone formation markers (BGP, ALP), resorption marker (OH-PRO) and serum 25(OH)D were measured at baseline after 18-months. All participants were divided into two groups according to the median variation of 25(OH)D over the observation period. RESULTS: SrR was associated with improvement of BMD at lumbar spine (p < 0.0001) and to a non significant variation at femoral neck (p = 0.2). Only subjects with Δ25(OH)D > 6.14 %, reported a significant BMD gain at femoral neck (p = 0.03). Change of BMD at femoral neck was positively associated with modification of ALP (r = 0.28, p = 0.01). This association was not maintained when considering only women with Δ25(OH)D < 6.14 % (r = 0.28, p = 0.09). At a multiple regression analysis, ALP change was the only predictor of femoral neck BMD modification (ß 0.13; SE 0.05; p = 0.01). CONCLUSION: Improvement of vitamin D status was associated with enhancement of BMD response to SrR in women with postmenopausal osteoporosis, in particular, at femoral neck.

Subclinical hypercortisol-assessment of bone fragility: experience of single osteoporosis center in Sicily.

AIM: Hypercortisolism is known to cause osteoporosis. Some evidence suggests that osteoporotic fractures may be the presenting manifestations of otherwise-asymptomatic hypercortisolism. The aim of our research was to investigate the prevalence of subclinical hypercortisolism (SH) in postmenopausal women evaluated for bone fragility. PATIENTS AND METHODS: One hundred consecutive postmenopausal women attending the Osteoporosis Centre in the Department of Internal Medicine of the University of Messina (Messina, Italy), for the first time, were screened and a total of 50 patients (age 58±5 years) were studied. Hypercortisolism was diagnosed by unsuppressed serum cortisol levels after 2 day low dose dexamethasone suppression test. RESULTS: Among the 50 postmenopausal women studied, 3 had SH. This prevalence was 6%. The three patients with SH had a normal bone mineral density (BMD) at lumbar spine and were osteopenic at femoral neck, and presented one or more vertebral fractures at spinal radiography. CONCLUSIONS: Physicians should always consider SH among the causes of bone fragility, especially in individuals with vertebral fractures and the presence of an only slightly reduced BMD.

Phalangeal quantitative ultrasound and metabolic control in pre-menopausal women with type 1 diabetes mellitus.

BACKGROUND: Several studies have reported increased fracture risk in Type 1 diabetes mellitus (T1DM). Quantitative Ultrasound (QUS) provides information on the structure and elastic properties of bone, which are important determinants of fracture risk, along with bone mineral density. AIM: To study phalangeal sites by QUS, examine bone turnover markers and analyze association between these factors with metabolic control in a population of pre-menopausal women with T1DM. MATERIAL AND METHODS: Thirty-five T1DM pre-menopausal women (mean age 34.5 ± 6.8 yr) attending the Diabetic Outpatients Clinic in the Department of Internal Medicine, University of Messina, were consecutively enrolled and divided into two groups, taking into account the mean value of glycated hemoglobin in the last three years. Twenty healthy age-matched women served as controls. Phalangeal ultrasound measurements [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), TScore, Z-Score] were performed using a DBM Sonic Bone Profiler. Osteocalcin and deoxypyridinoline served as markers of bone formation and bone resorption, respectively. RESULTS: T1DM women with poor metabolic control showed lower phalangeal QUS values compared to healthy controls (p<0.01) and T1DM women with good metabolic control (p<0.05). No significant differences in QUS measurements were detected between T1DM women with good metabolic control and healthy controls. Lower bone formation and increased bone resorption, although not statistically significant, were observed in patients with poor metabolic control in comparison to patients with good metabolic control. CONCLUSIONS: Poor metabolic control may worsen the quality of bone in T1DM. Phalangeal QUS could be considered as a tool to screen T1DM women for osteoporosis in pre-menopausal age.

Adrenal effects of teriparatide in the treatment of severe postmenopausal osteoporosis.

UNLABELLED: The aim of our study was to investigate the effects of teriparatide on the hypophysis-adrenal axis in postmenopausal women. Treatment with teriparatide increased plasmatic and urinary levels of cortisol after 6 and 12 months. Our paper demonstrates a possible direct secretagogue effect of teriparatide on adrenals in osteoporotic postmenopausal women. INTRODUCTION: Teriparatide, recombinant human parathyroid hormone (1-34) (rhPTH [1-34]), is approved for the treatment of osteoporosis in men and postmenopausal women at high risk for fracture. In literature, data regarding the secretagogue effect of PTH on adrenocortical cells are present on in vitro, but not on in vivo, studies. The aim of our study was to investigate the effects of teriparatide on the hypophysis-adrenal axis in postmenopausal women. METHODS: Twenty postmenopausal women with severe osteoporosis were treated with teriparatide in a regimen of 20 µg daily, self-administered injections at bedtime for 12 months and a calcium and vitamin D supplementation. At the same time, 20 osteopenic women matched for age and body mass index with the patients were enrolled and treated only with calcium and vitamin D. In all subjects, calcium, adrenocorticotropic hormone (ACTH), and plasmatic and urinary cortisol were evaluated at baseline and after 6 and 12 months. RESULTS: Treatment with teriparatide increased plasmatic and urinary levels of cortisol after 6 and 12 months, reaching statistical significance only after 1 year. Plasmatic levels of ACTH did not change significantly. CONCLUSIONS: Our paper, for the first time, demonstrates a possible direct secretagogue effect of teriparatide on adrenals in osteoporotic postmenopausal women.

Non smoking for successful aging: therapeutic perspectives.

The smoke of cigarettes represents an important accelerator of the aging process, and there is no doubt that smoke is an important risk factor for many diseases, in particular for cardiovascular, neoplastic and respiratory diseases. Smoking plays an important role also in the development of other pathological conditions being particularly frequent in geriatric ages, such as dementia, osteoporosis, diabetes, erectile dysfunction, senile macular degeneration, nuclear cataract and alterations of skin. This means that smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autonomy. Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. The first requirement of stopping smoking certainly is the motivation of the smoker himself to do this, since without this motivation any attempt is futile. Today numerous quitting strategies exist, either of pharmacological or non-pharmacological type, which are also advantageous for the elderly person. Approved pharmacological treatments include nicotine replacement therapies, bupropion, drugs targeting cannabinoid receptors and newer pharmacological approaches including the selective nicotinic partial agonists. Varenicline, an alpha4 beta2 nicotinic acetylcoline receptor partial agonist, is the most recently agent approved for smoking cessation. This drug works by reducing the strength of the smoker's urge to smoke and by relieving withdrawal symptoms. The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioural and/or cognitive counselling to improve abstinence rates.

Haemostatic effects of phytoestrogen genistein in postmenopausal women.

INTRODUCTION: Genistein is an isoflavone phytoestrogen derived from the soybean which acts as natural selective estrogen receptor modulator. Various studies have pointed out its cardioprotective role. The aim of the study was to evaluate the haemostatic effects of genistein in postmenopausal women. MATERIAL AND METHODS: In this double-blind placebo-controlled trial we enrolled 104 healthy postmenopausal women with osteopenia. 53 patients (mean age 54.9+/-4.2 yr; BMI 23.4+/-3.2 Kg/m(2)) received genistein (54 mg/day) and 51 patients (mean age 55.4+/-4.3 yr; BMI 23.6+/-3.6 Kg/m(2)) received an identical placebo-tablet. Both groups received a calcium and vitamin D supplement. Plasma levels of D-dimer (DD), plasminogen activator inhibitor-1 (PAI-1) and prothrombin fragment 1+2 (F1+2) were measured at baseline and after 6 and 12 months of treatment. RESULTS: Baseline characteristics of the two groups were similar. Compared with placebo, genistein decreased significantly DD (p<0.001), but did not affect PAI-1 and F 1+2 plasma levels. CONCLUSION: The results of our study do not confirm effects of genistein on activation of the haemostatic system, but on the contrary the significant decrease of DD could indicate a possible cardioprotective role of genistein in postmenopausal women.

Bisphosphonates in the treatment of thalassemia-associated osteoporosis.

Thalassemia major is a common cause of skeletal morbidity, as shown by the increased fracture risk in thalassemic patients. The etiology of this bone disease is multifactorial and culminates in a state of increased bone turnover with excessive bone resorption and remodeling. Despite hormonal replacement therapy, calcium and vitamin D administration, effective iron chelation, and normalization of hemoglobin levels, patients with thalassemia major continue to lose bone mass. The increased bone turnover rate observed in thalassemic patients justifies the use of powerful anti-resorption drugs, such as bisphosphonates. To date, alendronate, pamidronate, and zoledronate seem to be effective in increasing bone mineral density and normalizing bone turnover, but more trials are necessary to evaluate their efficacy in reducing fracture risks in larger thalassemic populations.

Disappearance of a virilizing adrenal tumor following therapy with cyproterone acetate.

A 57-year-old woman presented with an apparently obvious diagnosis of iatrogenic virilization. At the age of 51, she began a 4-year treatment with prednisone or cyclosporine, which are known to promote hair growth, for Behçet disease. At the age of 56, osteoporosis was overtreated with the anabolic steroid nandrolone. Insignificant inhibition by dexamethasone of the extremely high serum concentrations of testosterone and less high concentrations of weak androgens prompted us to search for a virilizing tumor. Computed tomography showed a 2.3 x 1.5 cm nodule in the right adrenal gland. As the patient refused surgery, virilization was treated with the antiandrogen cyproterone acetate (CPA), but for only 4 months because clinical and hormone abnormalities reversed and the tumor was no longer visible. The patient remains symptom-free. This first report of a curative effect of CPA on a purely virilizing adrenal tumor opens new avenues in the management of such tumors.

Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear factor-kB ligand system play a role?

Multiple factors can contribute to the development of osteodystrophy in patients with chronic liver disease (CLD). Recently, two new cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor-kB ligand (RANKL), have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Therefore, the aim of our study was to evaluate bone metabolism, bone mineral density (BMD) and OPG/RANKL system in 65 male patients with CLD and in 65 healthy controls. Our patients showed lower BMD values than controls both at lumbar and femoral levels. Moreover, they had an unbalanced bone turnover with an increased resorption phase, as shown by high levels of urinary deoxypyridinoline and a decreased formation phase, as shown by the slightly, but significant, low levels of bone-alkaline phosphatase. Patients showed lower plasma levels of free-testosterone than controls and higher - although not significantly so - plasma levels of 17 beta-estradiol. Furthermore, patients with CLD had higher levels of sex hormone-binding globulin and OPG, and lower levels of 25-hydroxyvitamin D (25-HOD) and IGF-I than the control group, while RANKL levels were similar in the two groups. In conclusion, our data do not confirm the hypothesis that the OPG/RANKL system could exert a key role in the pathogenesis of hepatic osteodystrophy, but rather that the observed increase in OPG levels may represent either the result of the inflammatory process per se or a compensation for the observed enhanced bone resorption.

Effects of a long-term treatment with raloxifene on insulin sensitivity in postmenopausal women.

AIMS/HYPOTHESIS: Our aim was to investigate the effect of long-term administration of raloxifene, a selective estrogen receptor modulator, on insulin sensitivity, glucose tolerance and plasma lipid concentrations in a group of postmenopausal women. METHODS: A total of 24 women with postmenopausal osteoporosis were consecutively enrolled and randomly assigned to take raloxifene, 60 mg/day for 12 months or placebo. At baseline and after 6 and 12 months, in each subject insulin sensitivity (M-index) was assessed by means of an euglycaemic hyperinsulinaemic clamp. Plasma concentrations of total cholesterol, triglycerides and HDL-cholesterol were also measured and glucose tolerance was evaluated. RESULTS: In the raloxifene-treated group, the M index decreased after 6 and 12 months with respect to the placebo group (-21%, p=0.042 and -23%, p=0.018, respectively). Neither fasting plasma glucose nor glucose tolerance changed in the raloxifene-treated group, compared to the placebo group. Low density lipoprotein cholesterol concentrations decreased at 12 months (-13%, p=0.047). CONCLUSION/INTERPRETATION: A long-term treatment with raloxifene in osteoporotic, otherwise healthy post-menopausal women can reduce insulin sensitivity without affecting glucose tolerance.

Long-term hemostatic effects of cholesterol-lowering therapy with atorvastatin.

This study assessed hemostatic effects of an HMC-CoA reductase inhibitor, atorvastatin, on different parameters in 32 hypercholesterolemic patients of both sexes. In the patients and in 25 control subjects, plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor (PAI-1), D-dimer, prothrombin fragment 1 + 2 (F1 + 2), total cholesterol, triglycerides and fibrinogen had been measured. All these parameters were evaluated in patients after 6 and 12 months of treatment with atorvastatin at a dosage of 20 mg/day. This treatment significantly lowered the total cholesterol level in all patients. Moreover, after 6 months of atorvastatin treatment, PAI-1 and F1 + 2, which were both increased at baseline, were significantly reduced. This reduction continued after 12 months. The present results show that a reduction of hemostatic abnormalities, which exist in hypercholesterolemia, may be another important effect of the atorvastatin therapy.

Three-year effectiveness of intravenous pamidronate versus pamidronate plus slow-release sodium fluoride for postmenopausal osteoporosis.

All currently available and approved therapies for osteoporosis inhibit bone resorption. But, despite their great value, antiresorptive agents are generally not associated with dramatic increases in bone mass. In light of these data, the aim of our prospective, placebo-controlled, randomized clinical trial, with a 3-year follow up, was to examine the effects of cyclic intravenous pamidronate and fluoride in combination, versus pamidronate alone, on bone mineral density (BMD) at vertebral and femoral levels, biochemical markers of bone turnover, IGF-1 serum levels, and safety and tolerability in 40 postmenopausal women with osteoporosis. During the treatment period, pamidronate alone reduced both markers of bone formation and bone resorption, resulting in an increase of BMD, after 3 years, of 7.07% at the lumbar level and of 6.76% at the femoral level. In the group treated with pamidronate and fluoride, markers of bone turnover had a different trend: after 3 years, there was a lower reduction of bone resorption and an increase of bone formation markers, with a concomitant increase in IGF-1 levels. This resulted, after 3 years of treatment, in a marked variation of BMD at the lumbar level (+12.74%) and a reduced, but still significant, increase at the femoral level (3.89%). Spine radiography and clinical evaluation did not reveal any vertebral fractures in either treatment group. In conclusion, the combined use of pamidronate and fluoride produced somewhat larger, continuous increases in BMD, at the lumbar level, than pamidronate alone.

Hemostasis and fibrinolysis factors in first-degree relatives of patients with Type 2 diabetes without hypertension.

First-degree relatives of type 2 diabetic patients with or without a family history of hypertension are at increased risk for cardiovascular diseases. The aim of this study was to verify some possible hemostatic alterations in first-degree relatives of type 2 diabetic, normotensive and hypertensive patients. In 78 non-diabetic, normotensive first-degree relatives of type 2 diabetic patients (47 without a family history of hypertension and 31 with a family history of hypertension) and in 36 normoglycemic, normotensive subjects with no family history of hypertension, we evaluated plasma levels of fasting glucose and insulin, tissue-type plasminogen activator (t-PA), plasminogen activator-inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1 + 2 (F1+2). Insulin resistance, calculated by the HOMA model, and plasma levels of t-PA and PAI-1 were significantly higher in relatives of diabetics compared to controls. As far as the thrombin activation indexes are concerned, we detected a significant increase in DD and F1+2 in relatives of diabetics with hypertension compared to other study subjects. In conclusion, our data indicate that familial predisposition may influence the hemostatic system in first-degree relatives of diabetic and/or hypertensive patients.

Effects of long-lasting raloxifene treatment on serum prolactin and gonadotropin levels in postmenopausal women.

OBJECTIVE: To evaluate the effects of a 6 month administration of raloxifene hydrochloride, a selective estrogen receptor modulator which was recently approved for the prevention of osteoporosis, on serum gonadotropin and prolactin (PRL) levels and on TRH-stimulated PRL responsiveness in postmenopausal women who have not undergone estrogen replacement therapy. DESIGN AND METHODS: Sixteen healthy postmenopausal women were divided into two groups on the basis of their bone status, evaluated by dual energy X-ray absorptiometry at the lumbar level. Eight women (chronological age 52.4+/-4.1 (s.d.) years, menopausal age 42.4+/-3.9 years), in whom T-score L2-L4 was less than -2.5 s.d., were treated with raloxifene (60 mg p.o.) administered daily for 6 months (group 1), while the other eight women (chronological age 52.6+/-2.5 years, menopausal age 42.1+/-3.6 years), in whom the T-score L2-L4 ranged between -1 and -2.5 s.d., were used as a control group (group 2). Serum PRL, FSH, LH and 17beta-estradiol (E2) levels were evaluated at baseline and after 3 and 6 months of treatment. In all subjects, PRL responsiveness to TRH (200 microg i.v.) administration was evaluated at baseline and at the end of the study. RESULTS: At baseline, mean PRL, LH and FSH levels were not significantly different in the two groups (PRL 133.6+/-21.7 vs 136.7+/-28.1 mIU/l (NS), LH 25.1+/-6.8 vs 24.4+/-6.7 mIU/ml (NS), FSH 74.4+/-25.0 vs 71.1+/-24.1 mIU/ml (NS), in group 1 and group 2 respectively). No significant variations in serum FSH and LH values, in either group, or in serum PRL levels in group 2, were observed at the 3 and 6 month examinations. On the contrary, serum PRL values decreased significantly in group 1 after 3 months (100.1+/-47.7 mIU/l, P<0.05) and 6 months (81.5+/-30.2 mIU/l, P<0.001). At baseline, no significant differences were observed in the TRH-stimulated serum PRL peak between the groups (1015.4+/-30.5 vs 1030.2+/-25.7 mIU/l in group 1 and in group 2 respectively), while it decreased significantly at the 6 month examination in group 1 (770.5+/-47.4 mIU/l, P<0.001) and it was significantly lower than in group 2 (1068.1+/-301.8 mIU/l, P=0.02). Serum E2 was not detected at baseline and at each examination, in all patients. CONCLUSIONS: The decrease of PRL values induced by long-term raloxifene administration in postmenopausal women could be explained by a direct antiestrogenic effect of raloxifene on lactotrope cells or by the recently suggested increase of opiatergic tone on the hypothalamic-pituitary region.

Bisphosphonates in the treatment of thalassemia-induced osteoporosis.

The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years' daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 +/- 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients.