Dietary supplementation with omega-3 in cystic fibrosis patients

Accumulation of neutr ophils releasing proteolytic enzymes and free radicals induceprogressive lung tissue destruction in CF. Among several hfflammatory mediatorsimplicated in this process, leukotriene B 4 (LTB4) product of arachidonic (AA;20:4n 6) omega 6 polytmsaturated fatty acid (PUFA) plays an important role.Various anti inflammatory strategies including dietary supplementation of omega 3PUFA, known to favor the synthesis of less active leukotriene B 5 (LTBs), have beeninvestigated. To further explore this nutritional approach, biological effects of anomega 3 PUFA oral supplementation (n 3 OS) were measured in 17 CF patients haa prospective, randomized, double blind, crossover study. CF patients (mean age:18 + 9 years, FEVI: 66 + 29 %) received a dietary supplementation enriched, or not,ha omega 3 PUFA during a 2 x 6 months period. A modification in neutrophilmembrane PUFA composition was observed under n 3 OS with an increase in EPA(20:5n 3) PUFA (from 0.66 ± 0.56 to 1.60 ± 0.61 ~tmol %, P< 0.01). The LTB jLTB 5ratio was decreased (from 72 + 27 to 24 + 7, P< 0.C~31), in CF patients taking n 3OS. However, n 3 OS supplementation did neither affect the internalization of bothIL 8 receptors following IL 8 exposure, nor IL 8 induced neutrophil chemotaxis.Our results show that n 3 PUFA are absorbed and incorporated in neutrophilmembrmae. The consecutive decrease ha LTBjLTB 5 ratio suggests that, ha theseconditions, neutr ophils may produce less toxic mediators from the AA pathway. Thepotential clinical benefit for CF patients still needs to be assessed with furtherstudies of longer duration and including more patients.

Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline.

The prevalence of obesity is rising progressively, even among older age groups. By the year 2030-2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years and older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20 and 30% dependent on the model used. This means 20.9 million obese 60+ people in the USA in 2010 and 32 million obese elders in 2015 in the EU. Although cut-off values of BMI, waist circumference and percentages of fat mass have not been defined for the elderly (nor for the elderly of different ethnicity), it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a BMI above 30 kg/m(2). Thus, treatment should only be offered to patients who are obese rather than overweight and who also have functional impairments, metabolic complications or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should aim to minimize muscle and bone loss but also vigilance as regards the development of sarcopenic obesity - a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone - is important in the elderly, who are vulnerable to this outcome. Life-style intervention should be the first step and consists of a diet with a 500 kcal (2.1 MJ) energy deficit and an adequate intake of protein of high biological quality together with calcium and vitamin D, behavioural therapy and multi-component exercise. Multi-component exercise includes flexibility training, balance training, aerobic exercise and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older have been excluded.

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients.

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor.

Risk of prostate, breast and colorectal cancer after skin cancer diagnosis.

Ultraviolet radiation is the major cause of skin cancer, but promotes vitamin D synthesis, and vitamin D has been inversely related to the risk of several common cancers including prostate, breast and colorectum. We therefore computed the incidence of prostate, breast and colorectal cancer following skin cancer using the datasets of the Swiss cancer Registries of Vaud and Neuchâtel. Between 1974 and 2005, 6,985 histologically confirmed squamous cell skin cancers, 21,046 basal cell carcinomas and 3,346 cutaneous malignant melanomas were registered, and followed up to the end of 2005 for the occurrence of second primary cancer of the prostate, breast and colorectum. Overall, 680 prostate cancers were observed versus 568.3 expected (standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI): 1.11-1.29), 440 breast cancers were observed versus 371.5 expected (SIR = 1.18; 95% CI: 1.08-1.30) and 535 colorectal cancers were observed versus 464.6 expected (SIR = 1.15; 95% CI: 1.06-1.25). When basal cell, squamous cell and skin melanoma were considered separately, all the SIRs for prostate, breast and colorectal cancers were around or slightly above unity. Likewise, the results were consistent across strata of age at skin cancer diagnosis and location (head and neck versus others), and for male and female colorectal cancers. These findings, based on a population with a long tradition of systematic histologic examination of all surgically treated skin lesions, do not support the hypothesis that prostate, breast and colorectal cancer risk is decreased following skin cancer.

Six Years of Denosumab Treatment in Postmenopausal Women with Osteoporosis: Results From the First Three Years of the FREEDOM Extension

Background/Purpose: Denosumab (DMAb) is an approved therapy for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. A favorable risk/benefit profile was demonstrated in the pivotal, 3-year FREEDOM trial (Cummings et al NEJM 2009). The open-label, active-treatment FREEDOM Extension study is investigating the efficacy and safety of DMAb for up to 10 years. The Extension trial enrolled women who had received DMAb or placebo in FREEDOM and provides an opportunity to evaluate the long-term efficacy and safety of continuous DMAb treatment (long-term group), and to replicate the DMAb findings observed in FREEDOM (cross-over group). Here, we report the results from the first 3 years of the Extension, representing up to 6 continuous years of DMAb exposure. Methods: During the Extension, each woman is scheduled to receive 60 mg DMAb every 6 months and supplemental calcium and vitamin D daily. For the analyses reported here, women from the FREEDOM DMAb group received 3 more years of DMAb for a total of 6 years of exposure (long-term group) and women from the FREEDOM placebo group received 3 years of DMAb exposure (cross-over group). Results: Of the 5928 women eligible for the Extension, 4550 (77%) enrolled (N_2343 long-term; N_2207 cross-over). In the long-term group, further significant mean increases in bone mineral density (BMD) occurred 4044 for cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip (Figure). During the first 3 years of DMAb treatment during the Extension, the cross-over group had significant mean gains in BMD at the lumbar spine (9.4%) and total hip (4.8%), similar to those observed in the long-term DMAb group during the first 3 years of FREEDOM (lumbar spine, 10.1%; total hip, 5.7%). Serum CTX was rapidly and similarly reduced after the 1st (cross-over) or 7th (long-term) DMAb dose with the characteristic attenuation observed at the end of the dosing period. In the cross-over group, yearly incidences of new vertebral and nonvertebral fractures were lower than in the FREEDOM placebo group. Fracture incidence remained low in the long-term group. Incidences of adverse events (AEs) and serious AEs did not increase over time with DMAb treatment. There were 2 subjects with AEs adjudicated to ONJ in the cross-over group and 2 in the long-term group. Both cases in the cross-over group healed completely and without further complications; 1 of these subjects continues to receive DMAb. Both women in the long-term group continue to be followed. No atypical femur fractures have been observed to date. Figure. Percent changes in bone mineral density during FREEDOM and the Extension Conclusion: DMAb treatment for 6 continuous years (long-term group) remained well tolerated, maintained reduced bone turnover, and continued to significantly increase BMD. Fracture incidence remained low. DMAb treatment for 3 years in the cross-over group reproduced the original observations in FREEDOM

Inducing effect of skeletal muscle extracts on the appearance of calbindin-immunoreactive dorsal root ganglion cells in culture.

Calbindin D-28k is a calcium-binding protein which is not expressed by dorsal root ganglion cells cultured from 6-day-old (E6) chick embryos. When soluble muscle extracts from embryos at E11, E18 or chickens 2 weeks after hatching were added immediately after seeding, dorsal root ganglia cells grown at E6 displayed neuronal subpopulations expressing calbindin immunoreactivity with time; the effect of muscle extract on the percentage of calbindin-immunoreactive dorsal root ganglia cells followed a dose-response curve. When muscle extract was added to cultures after a 3 day delay, the percentage of calbindin-expressing neurons was unchanged. The effect produced by muscle extract and, to a lesser degree, skin extract on the appearance of calbindin-positive neurons was not reproduced by brain or liver extracts while all four exerted a trophic action on cultured neurons. Hence it is assumed that muscle extract contains a factor which produces an inductive effect on the initiation of calbindin-expression by uncommitted subpopulations of sensory neurons rather than a trophic influence on the selective survival of covertly committed neuronal subpopulations. The fact that muscle extract promoted calbindin expression by dorsal root ganglia cells in neuron-enriched as well as in mixed dorsal root ganglion cell cultures indicates that the factor would act directly on sensory neurons rather than indirectly through mediation of non-neuronal cells. Since the active muscular factor was non-dialysable, heat-inactivated, trypsin-sensitive and retained by molecular filters with a cut-off of 30 K, this factor is probably a protein.

Musculoskeletal pain in female asylum seekers and hypovitaminosis D3

Résumé de l'article L'hypovitaminose D3 est bien connue et courante chez la population âgée en Occident. Toutefois, elle est probablement sous-diagnostiquée chez les jeunes femmes immigrantes, bien qu'elle soit bien documentée, principalement en Angleterre dans la population Indo-Pakistanaise. Lorsque ce déficit est diagnostiqué, le traitement substitutif est simple et bon marché. Nous avons suspecté une haute prévalence chez de jeunes femmes requérantes d'asile, surtout chez celles provenant de cultures différant quant à l'exposition solaire et la diète. Nous publions donc une série de 11 cas de patientes avec une hypovitaminose D symptomatique issues de la consultation générale de la Policlinique Médicale Universitaire. Toutes les patientes présentaient une anamnèse d'une faible exposition solaire et de douleurs osseuses diffuses, d'une fatigue, d'une faiblesse musculaire ou des modifications de la marche. Toutefois, les premiers diagnostics évoqués par les médecins étaient une possible somatisation (3 patientes), des douleurs dorso-lombaires chroniques (4 patientes) et des symptômes somatiques multiples et inexpliqués (3 patientes). Le diagnostic a été posé d'emblée chez une patiente seulement. La durée moyenne des plaintes avant la pose du diagnostic était de 38 mois et 5 jours. Avec le traitement de cholecalciférol et de calcium, les symptômes disparaissaient entre 1 et 3 mois, chez une patiente ils ont duré sept mois. Le taux moyen de 250H vitamine D3 était de 10.9 nmol/l (IR 21-131). Le taux moyen de calcium était de 2.19 mmol/l (2.15-2.55) et quatre patientes présentaient une hypocalcémie. Nous pensons donc que les femmes requérantes d'asile sont à risque d'une durée prolongée de symptômes, de part la possible haute prévalence de cette condition et la difficulté chez les médecins à la reconnaître. Le diagnostic d'hypovitaminose devrait être recherché chez les femmes requérantes d'asile souffrant de douleurs musculo-squelettiques de longue durée. Le premier diagnostic souvent évoqué, dans un contexte psychosocial souvent difficile, était de l'ordre d'un trouble somatoforme douloureux ou de somatisations. Toutefois, les douleurs liées à l'hypovitaminose D3 sont relativement bien définies ; elles sont symétriques, osseuses, débutent souvent dans la région lombaire pour ensuite s'étendre au bassin, aux membres inférieures proximalement et à la cage thoracique. Le traitement substitutif est simple, peu onéreux et il serait judicieux d'initier d'autres études pour évaluer le besoin d'une substitution de routine dans la population présentée. Abstract: Deficiency of vitamin D, which can lead to osteomalacia, is common in elderly patients in Western countries. However, it is still widely underdiagnosed in young immigrant women, even though the condition has been extensively reported in the immigrant Indo- Asian population in the United Kingdom since the 1960s. A recent study reports an average 59 months before diagnosis was established, and another study found a prevalence of 78% of hypovitaminosis D3 (compared with 58% in controls) in an Indo-Asian population attending a UK rheumatology clinic. When recognised, hypovitaminosis D3 is easily treatable. A study on osteomalacic myopathy in veiled Arabic women in Denmark found that muscle strength returned to normal (except in maximal voluntary con-traction) after six months' treatment. We expected to see this disease in female asylum seekers, especially in those from societies with different customs regarding exposure to sunlight and diet We report 11 cases of symptomatic hypovitaminosis D3 in female asylum seekers (table 1). We focus on the pathology encountered by the primary care doctors caring for these 11 patients, the length of time between the appearance of symptoms, and the establishment of the diagnosis of hypovitaminosis D3 as well as the women's response to treatment by the improvement of a wide range of clinical symptoms-bone pain, muscular weakness, and fatigue.

Les traitements de l'ostéoporose (à l'exception de la substitution hormonale et de ses dérivés) [Treatment of osteoporosis (with the exception of hormone replacement and its derivates]

Calcium and vitamin D supplementation are warranted for the treatment of osteoporosis, when other specific drugs are used. Vitamin D supplementation is necessary when the plasma level of 25-hydroxy-vitamin D is below 30 nmol/l (12 pg/l) in order to avoid any increase of the plasma parathyroid hormone level. Bisphosphonates are the most widely drugs used. Recent advances will provide patients with a more convenient therapeutically equivalent alternative: the once-weekly oral dosing regimen and probably the possibility to give infusions at intervals of up to one year. Parathyroid hormone administered subcutaneously daily produced a dramatic increase of trabecular and cortical bone mineral density, and an important decrease of vertebral and nonvertebral fracture risk. Strontium is a new original drug, which stimulates bone formation, and inhibits bone resorption. It significantly improves trabecular and cortical bone mass. Calcitonin not only prevents the recurrence of vertebral fractures, but possibly could decrease hip fractures risk. Hydrochlorothiazide preserves the bone mineral density, and decreases nonvertebral fracture risk, as showed in epidemiological studies. Large clinical trials with statins therapy in appropriate populations are required to find out whether these drugs have any role in preventing fractures.

Neuronal phenotypes in mouse dorsal root ganglion cell cultures: enrichment of substance P and calbindin D-28k expressing neurons in a defined medium.

The primary sensory neurons in mouse dorsal root ganglia consist of diversified subpopulations which express distinct phenotypic characteristics such as substance P or calbindin D-28k. To determine whether neuronal phenotypes are altered or not in in vitro cultures carried out in a defined synthetic medium, dissociated dorsal root ganglion cells from newborn mice were grown in the alpha-modified minimum essential medium either supplemented with 10% fetal calf serum or serum-free. About 80% of the neurons survived after 5 days of culture in both media, but only 35% or 65% were rescued after 12 days in serum-free or fetal calf serum supplemented medium, respectively. The neuronal subpopulations expressing substance P or calbindin D-28k displayed similar morphological properties in both media and a higher resistance to culture conditions than the whole neuronal cell population, especially in serum-free medium. It is therefore concluded that a defined synthetic medium offers reproducible conditions to culture dorsal root ganglion cells for at least 5 days, stimulates the expression of substance P and enriches preferentially neuronal phenotypes expressing substance P or calbindin D-28k, for a longer period of culture.

Substance P and calbindin D-28k-immunoreactivity in primary sensory neurons of chick embryos: differential neuronal birthdates and transient co-localization.

During the ontogenesis of dorsal root ganglia (DRG), the immunoreactivity to substance P (SP) and calbindin D-28k (CaBP) appears in chickens at embryonic day 5 (E5) and E10 respectively. To establish the birthdates of primary sensory neurons expressing SP or CaBP, chick embryos were given repetitive intra-amniotic injections of [3H]-thymidine. The neuroblasts giving rise to SP-expressing neurons were labeled up to E6 while those generating CaBP-immunoreactive neurons stopped to incorporate [3H]-thymidine before E5.5. This finding indicates that neurons exhibiting distinct phenotypes may originate from neuroblasts which arrest to proliferate at close but distinct stages of development. To determine whether SP and CaBP are co-expressed or not in DRG neurons, chick embryos at E12, E18, and chickens two weeks after hatching were perfused and fixed to detect simultaneously SP- and CaBP-immunoreactivity in DRG sections. The results showed that SP and CaBP were transiently co-expressed by a subset of neurons at E12. Later, however, the SP-immunoreactivity was gradually lost by these ganglion cells, so that the SP- and CaBP-immunoreaction defined two distinct neuronal subpopulations after hatching. In conclusion, most CaBP-immunoreactive DRG cells derive from a subset of neurons in which SP and CaBP are transiently co-localized.

A large-scale genetic validation study coupled with in vitro analyses reveal a role for vitamin Dsignaling in the pathogenesis and response to treatment of hepatitis C virus infection

Background and Aims: Vitamin D is an important modulatorof numerous cellular processes. Some of us recently observedan association of the 1a-hydroxylase promoter polymorphismCYP27B1-1260 rs10877012 with sustained virologic response (SVR)in a relatively small number of German patients with chronichepatitis C. In the present study, we aimed to validate thisassociation in a large and well characterized patient cohort, theSwiss Hepatitis C Cohort Study (SCCS). In addition, we examinedthe effect of vitamin D on the hepatitis C virus (HCV) life cyclein vitro.Methods: CYP27B1-1260 rs10877012 and IL28B rs12979860 singlenucleotide polymorphisms (SNPs) were genotyped in 1049 patientswith chronic hepatitis C from the SCCS, of whom 698 were treatedwith pegylated interferon-a (PEG-IFN-a) and ribavirin. In addition,112 patients with spontaneous clearance of HCV were examined.SNPs were correlated with variables reflecting the natural courseand treatment outcome of chronic hepatitis C. The effect of1,25-(OH)2D3 (calcitriol) on HCV replication and viral particleproduction was investigated in vitro using human hepatoma celllines (Huh-7.5) harbouring subgenomic replicons and cell culturederivedHCV.Results: The CYP27B1-1260 rs10877012 genotype was notassociated with SVR in patients with the good-response IL28Brs1279860 CC genotype. However, in patients with poor-responseIL28B rs1279860 genotype CT and TT, CYP27B1-1260 rs10877012was a significant independent predictor of SVR (15% difference inSVR between rs10877012 genotype AA vs. CC, p = 0.030, OR = 1.495,95% CI = 1.038-2.152). The CYPB27-1260 rs10877012 genotype wasneither associated with spontaneous clearance of HCV, nor withliver fibrosis progression rate, inflammatory activity of chronichepatitis C, or HCV viral load. Physiological doses of 1,25-(OH)2D3did not significantly affect HCVRNA replication or infectiousparticle production in vitro.Conclusions: The results of this large-scale genetic validationstudy reveal a role of vitamin D metabolism in the responseto treatment in chronic hepatitis C, but 1,25-(OH)2D3 does notexhibit a significant direct inhibitory antiviral effect. Thus, theability of vitamin D to modulate immunity against HCV shouldbe investigated.

Marqueurs biologiques des statuts vitaminiques B12 et D: aspects analytiques d'importance clinique [Biological markers for the status of vitamins B12 and D: the importance of some analytical aspects in relation to clinical interpretation of results].

Biological markers for the status of vitamins B12 and D: the importance of some analytical aspects in relation to clinical interpretation of results When vitamin B12 deficiency is expressed clinically, the diagnostic performance of total cobalamin is identical to that of holotranscobalamin II. In subclinical B12 deficiency, the two aforementioned markers perform less well. Additional analysis of a second, functional marker (methylmalonate or homocysteine) is recommended. Different analytical approaches for 25-hydroxyvitamin D quantification, the marker of vitamin D deficiency, are not yet standardized. Measurement biases of up to +/- 20% compared with the original method used to establish threshold values are still observed.

Zoledronic Acid in Reducing Clinical Fracture and Mortality after Hip Fracture.

BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS: The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction (P = 0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P = 0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P = 0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic-acid group (P = 0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. CONCLUSIONS: An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival. (ClinicalTrials.gov number, NCT00046254.).

Expression of calbindin immunoreactivity by subpopulations of primary sensory neurons in chick embryo dorsal root ganglion cells grown in coculture or conditioned medium.

Primary sensory neurons which innervate neuromuscular spindles in the chicken are calbindin-immunoreactive. The influence exerted by developing skeletal muscle on the expression of calbindin immunoreactivity by subpopulations of dorsal root ganglion (DRG) cells in the chick embryo was tested in vitro in coculture with myoblasts, in conditioned medium (CM) prepared from myoblasts and in control cultures of DRG cells alone. Control cultures of DRG cells grown at the 6th embryonic day (E6) did not show any calbindin-immunostained ganglion cell. In coculture of myoblasts previously grown for 14 days, about 3% of calbindin-immunoreactive ganglion cells were detected while about 1% were observed in some cultures grown in CM. Fibroblasts from various sources were devoid of effect. Skin or kidney cells were more active than myoblasts to initiate calbindin expression by subpopulations of DRG cells in coculture or, to a lesser degree, in CM. The results suggest that cellular factors would rather induce calbindin expression in certain sensory neurons than ensure a selective neuronal survival.

Place de ta vitamine D, du sevelamer et du cinacalcet dans la prise en charge des patients en insuffisance rénale [Treatment of secondary hyperparathyroidism in renal insufficiency: role of calcitriol, sevelamer and cinacalcet]

Along with the decrease in kidney function arises a secondary hyperparathyroidism, which constitutes one of the most important risk factor for mortality in patients suffering from renal insufficiency. Treating secondary hyperparathyroidism is challenging, as most of the parameters of mineral metabolism are interconnected. We review here the pathophysiology and treatment options of this entity.