Effect of increased serum 25(OH)D and calcium on structure and function of post-menopausal women: a pilot study.

The purpose was to determine if increasing serum 25(OH)D and calcium in postmenopausal women increased skeletal muscle size, strength, balance, and functional task performance while decreasing muscle fatigue. PCSA of the vastus lateralis increased and ascent of stairs time decreased after 6 months of increased serum 25(OH)D. PURPOSE: The Institute of Medicine recommends ≥ 20 ng/ml of serum 25-hydroxyvitamin D [25(OH)D] for bone and overall health. Serum 25(OH)D levels have been associated with physical performance, postural sway, and falls. The purpose of this study was to determine if increasing postmenopausal women's serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml improved skeletal muscle size, strength, balance, and functional performance while decreasing skeletal muscle fatigue. METHODS: Twenty-six post-menopausal women (60-85 years old) with baseline serum 25(OH)D levels between 20 and 30 ng/ml were recruited. Oral over-the-counter (OTC) vitamin D3 and calcium citrate were prescribed to increase subjects' serum 25(OH)D to levels between 40 and 50 ng/ml, serum calcium levels above 9.2 mg/dl, and PTH levels below 60 pg/ml, which were confirmed at 6 and 12 weeks. Outcome measures assessed at baseline and 6 months included muscle physiological cross-sectional area (PCSA), muscle strength, postural balance, time to perform functional tasks, and muscle fatigue. Repeated measures comparisons between baseline and follow-up were performed. RESULTS: Nineteen subjects completed the study. One individual could not afford the time commitment for the repeated measures. Three individuals did not take their vitamin D as recommended. Two subjects were lost to follow-up (lack of interest), and one did not achieve targeted serum 25(OH)D. Vastus lateralis PCSA increased (p = 0.007) and ascent of stair time decreased (p = 0.042) after 6 months of increasing serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml. Isometric strength was unchanged. Anterior-posterior center of pressure (COP) excursion and COP path length decreased (p < 0.1) albeit non-significantly, suggesting balance may improve from increased serum 25(OH)D and calcium citrate levels. CONCLUSIONS: Several measures of muscle structure and function were sensitive to elevated serum 25(OH)D and calcium levels indicating that further investigation of this phenomenon in post-menopausal women is warranted.

Intensive monitoring of post filter ionized calcium concentrations during CVVHD with regional citrate anticoagulation: A retrospective study.

BACKGROUND: The aim of the present study was to assess the predictive value of post-filter ionized calcium (pfCa) levels for filter-clotting during continuous veno-venous hemodialysis (CVVHD) with regional citrate anticoagulation (RCA). METHODS: Retrospective analysis of a database derived from 6 intensive care units (ICU) at a university hospital. During the 3-year period 1070 patients were treated with RCA-CVVHD with a citrate starting dose of 4 mmol/L blood and a target-range for pfCa of 0.25-0.35 mmol/L. RESULTS: The pfCa concentrations at RCA-CVVHD initiation were within the target range in 69.7% of patients. Within 12 h the fraction of patients with pfCa above target-range decreased significantly from 13.1% to 7.8% (p < .001). There was no significant difference in filter survival between patients with a pfCa initially below, within, or above the target-range (83.7%, 89.5% and 90.4%; p = .228) and no significant correlation between the last pfCa and the incidence of filter clotting (rho 0.018, p = .572 and -0.054, p = .104; respectively). CONCLUSIONS: CVVHD with a citrate starting dose of 4 mmol/L blood resulted in a pfCa within target in the majority of patients. The observation that pfCa was not associated with the incidence of circuit clotting suggests that less frequent measurements of pfCA might be safe.

Fracturas vertebrales múltiples postsuspensión de denosumab: revisión del tema a partir de dos casos clínicos / Discontinuation of denosumab and multiple vertebral fractures: report of two cases and review of the literature

Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)

The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)

Chronic Ingestion of Sodium and Potassium Bicarbonate, with Potassium, Magnesium and Calcium Citrate Improves Anaerobic Performance in Elite Soccer Players.

Anaerobic power and anaerobic capacity significantly influence performance in many sport disciplines. These include prolonged sprints in athletics, swimming, or cycling, and other high intensity intermittent sports, such as soccer or basketball. Considering the association of exercise-induced acidosis and fatigue, the ingestion of potential buffering agents such as sodium bicarbonate, has been suggested to attenuate metabolic acidosis and improve anaerobic performance. Since elite soccer players cover from 200 to 350 m while sprinting, performing 40⁻60 all out sprints during a game, it seems that repeated sprint ability in soccer players is among the key components of success. In our experiment, we evaluated the effectiveness of chronic supplementation with sodium and potassium bicarbonate, fortified with minerals, on speed and speed endurance in elite soccer players. Twenty-six soccer players participated in the study. The subjects were randomly divided into two groups. The experimental group was supplemented with sodium bi-carbonate and potassium di-carbonate fortified with minerals, while the control group received a placebo. The athletes were tested at baseline and after nine days of supplementation. Anaerobic performance was evaluated by the Repeated Anaerobic Sprint Test (RAST) protocol which involved 6 × 30 m max sprints, separated by 10 s of active recovery. Resting, post ingestion and post exercise concentrations of HCO3- and blood pH were measured as well as lactate concentration. The current investigation demonstrated a significant increase in RAST performance of elite soccer players supplemented with sodium and potassium bicarbonate along with calcium phosphate, potassium citrate, and magnesium citrate ingested twice a day over a nine-day training period. The improvements in anaerobic performance were caused by increased resting blood pH and bicarbonate levels.

Postmarketing experience with Neutrolin® (taurolidine, heparin, calcium citrate) catheter lock solution in hemodialysis patients.

Catheter-related bloodstream infections (CRBSI) are major complications for patients with life-threatening conditions requiring chronic vascular catheterization. The wide range of etiologic microbes and the ongoing development of resistance to antimicrobials with specific mechanisms of action make this an appropriate target for applying a nonspecific antimicrobial therapeutic. Taurolidine hydrolyzes into two antimicrobial moieties, formaldehyde and methylene glycol, which react with microbial surfaces. Neutrolin® (taurolidine, heparin, calcium citrate) was recently introduced in Germany as an antimicrobial catheter lock solution. This postmarketing experience collected data on 201 patients at 20 centers from January 2014 through September 2016. Likely CRBSI was observed in 13 episodes in 47,118 days (0.2759 per 1000 days [0.1468, 0.4718]). Thrombosed catheter was observed in seven catheters in 47,118 days (0.1486 per 1000 days [0.0595, 0.3061]). No adverse drug reactions that led to the discontinuation of Neutrolin® use were reported. Two patients experienced occasional transient dysgeusia. Neutrolin®, when used in conjunction with guideline-based catheter care, showed reduction in the rate of both CRBSI and catheter thrombosis relative to recent historical controls.

Acute and 3-month effects of calcium carbonate on the calcification propensity of serum and regulators of vascular calcification: secondary analysis of a randomized controlled trial.

SUMMARY: Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50. INTRODUCTION: Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification. METHODS: We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study. RESULTS: T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = -0.32, p = 0.05) and 8 h (r = -0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02). CONCLUSIONS: These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which calcium supplements might influence vascular calcification.

Acute effects of calcium citrate with or without a meal, calcium-fortified juice and a dairy product meal on serum calcium and phosphate: a randomised cross-over trial.

Ca supplements, but not dietary Ca, have been associated with increased cardiovascular risk. This difference could be related to differences in their acute effects on serum Ca. We therefore examined the effects of Ca from different sources on serum Ca and phosphate in a randomised, cross-over trial of ten women (mean age of 69 years). Fasting participants received a single dose of 500 mg of Ca as citrate, citrate with a meal, fortified juice or a dairy product meal, with at least 6 d between each intervention. Blood was sampled before and 1, 2, 4 and 6 h after each intervention was ingested. Serum ionised and total Ca increased significantly from baseline over 6 h. Using calcium citrate fasting as a comparator, the elevations in ionised and total Ca were similar after fortified juice, delayed after calcium citrate with a meal and smaller after a dairy product meal. Serum phosphate and calcium-phosphate product increased from baseline after calcium citrate with a meal and after a dairy product meal, and they declined after calcium citrate fasting and after fortified juice. The elevations in serum Ca in the present study were only slightly different from those observed after the administration of 1000 mg of Ca in a previous study. These data indicate that different sources of Ca have different acute effects on serum Ca and support recommendations that dietary Ca might be safer than supplements. Whether these differences contribute to differences in cardiovascular risk requires further study.

Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women.

OBJECTIVE: This study aims to prospectively assess the incidence of hypercalciuria and hypercalcemia with different doses of vitamin D and with a calcium intake of approximately 1,200 mg/day. METHODS: This was a 1-year randomized placebo-controlled study of vitamin D (400-4,800 IU/d) in 163 white women aged 57 to 90 years. Calcium citrate tablets (200 mg) were added to the diet to achieve a total calcium intake of approximately 1,200 mg/day in all groups. All women had vitamin D insufficiency at baseline, with serum 25-hydroxyvitaminD levels lower than 20 ng/mL (50 nmol/L). Serum and 24-hour urine calcium were collected every 3 months on supplementation, any test result above the upper reference range represented an episode of hypercalcemia or hypercalciuria. Mixed-effects models and multivariate logistic regression were used in the analysis. RESULTS: Hypercalcemia (>10.2 mg/dL [2.55 mmol/L]) occurred in 8.8% of white women. Hypercalciuria (>300 mg/d [7.5 mmol]) occurred in 30.6% of white women. Episodes of hypercalciuria were transient in half of the group and recurrent in the other half. No relationship between hypercalcemia or hypercalciuria and vitamin D dose was found, and hypercalciuria was equally common in the placebo group. CONCLUSIONS: Hypercalciuria and hypercalcemia commonly occur with vitamin D and calcium supplements. Whether hypercalciuria and hypercalcemia are caused by calcium, vitamin D, or both is unclear. These findings may have relevance to the reported increase in kidney stones in the Women's Health Initiative trial. Because calcium 1,200 mg and vitamin D 800 IU/day are widely recommended in postmenopausal women, systematic evaluation of the safety of supplements is warranted in clinical management and in future studies.

Hypocalcaemia following thyroidectomy unresponsive to oral therapy.

Hypocalcaemia due to hypoparathyroidism following thyroidectomy is a relatively common occurrence. Standard treatment is with oral calcium and vitamin D replacement therapy; lack of response to oral therapy is rare. Herein we describe a case of hypoparathyroidism following thyroidectomy unresponsive to oral therapy in a patient with a complex medical history. We consider the potential causes in the context of calcium metabolism including: poor adherence, hungry bone syndrome, malabsorption, vitamin D resistance, bisphosphonate use and functional hypoparathyroidism secondary to magnesium deficiency. Malabsorption due to intestinal hurry was likely to be a contributory factor in this case and very large doses of oral therapy were required to avoid symptomatic hypocalcaemia.

A target-oriented algorithm for citrate-calcium anticoagulation in clinical practice.

BACKGROUND/AIMS: Because of a high monitoring demand and an ensuing need for automation of regional citrate anticoagulation (RCA), a new semi-automated target-oriented algorithm was developed. The aim of this study was the evaluation of its functionality and safety. METHODS: Fourteen haemodialysis patients were treated 5 times consecutively with RCA. Samples were drawn pre- and post-infusion once per hour. Electrolytes, blood cell counts, acid-base and coagulation parameters were analyzed. RESULTS: Mean ionized calcium (Ca(2+)) values pre-filter were 0.23 and 0.33 mmol/l in the 0.2 and 0.3 mmol/l target groups, respectively. Extraction ratios for citrate and total calcium through the dialysis filter were constant during the entire treatment (83 and 68%, respectively). Citrate accumulation was avoided. CONCLUSION: The new algorithm enables safe and accurate RCA. By regulating Ca(2+) pre-filter using the target-oriented algorithm, the degree of anticoagulation may be easily controlled.

Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study.

BACKGROUND: Hypoparathyroidism results in impaired mineral homoeostasis, including hypocalcaemia and hyperphosphataemia. Treatment with high-dose oral calcium and active vitamin D does not provide adequate or consistent control of biochemical indices and can lead to serious long-term complications. We aimed to test the efficacy, safety, and tolerability of once-daily recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) in adults with hypoparathyroidism. METHODS: In this double-blind, placebo-controlled, randomised phase 3 study (REPLACE), we recruited patients with hypoparathyroidism (≥ 18 months duration) aged 18-85 years from 33 sites in eight countries. After an optimisation period, during which calcium and active vitamin D doses were adjusted to achieve consistent albumin-corrected serum calcium, patients were randomly assigned (2:1) via an interactive voice response system to 50 µg per day of rhPTH(1-84) or placebo for 24 weeks. Active vitamin D and calcium were progressively reduced, while rhPTH(1-84) could be titrated up from 50 µg to 75 µg and then 100 µg (weeks 0-5). The primary endpoint was the proportion of patients at week 24 who achieved a 50% or greater reduction from baseline in their daily dose of oral calcium and active vitamin D while maintaining a serum calcium concentration greater than or the same as baseline concentrations and less than or equal to the upper limit of normal, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00732615. FINDINGS: Between June 23, 2009, and Feb 28, 2011, 134 eligible patients were recruited and randomly assigned to rhPTH(1-84) (n=90) or placebo (n=44). Six patients in the rhPTH(1-84) group and seven in the placebo group discontinued before study end. 48 (53%) patients in the rhPTH(1-84) group achieved the primary endpoint compared with one (2%) patient in the placebo group (percentage difference 51.1%, 95% CI 39.9-62.3; p<0.0001). The proportions of patients who had at least one adverse event were similar between groups (84 [93%] patients in the rhPTH[1-84] group vs 44 [100%] patients in the placebo group), with hypocalcaemia, muscle spasm, paraesthesias, headache, and nausea being the most common adverse events. The proportions of patients with serious adverse events were also similar between the rhPTH(1-84) group (ten [11%] patients) and the placebo group (four [9%] patients). INTERPRETATION: 50 µg, 75 µg, or 100 µg per day of rhPTH(1-84), administered subcutaneously in the outpatient setting, is efficacious and well tolerated as a PTH replacement therapy for patients with hypoparathyroidism.

Acute effect of calcium citrate on serum calcium and cardiovascular function.

Calcium supplements have been associated with an increased risk of cardiovascular events. However, the validity of these findings has been questioned. A major concern is that the mechanism underlying an increase in cardiovascular events has not been demonstrated. Calcium initiates cardiac and vascular contraction following influx of calcium into cardiac and smooth muscle from extracellular fluid. We have investigated whether the acute rise in serum calcium following calcium supplement administration is associated with adverse changes in cardiovascular function. In an open interventional study, we recruited 25 volunteers (16 female, age 60.3 ± 6.5 years, body mass index 25.7 ± 2.7 kg/m2) from the community who were not taking calcium supplements. Participants were studied before and 3 hours after a single oral dose of 1000 mg calcium citrate. We assessed well-validated markers of arterial stiffness (pulse wave velocity [PWV]), arterial wave reflection (augmentation index [AIx]), and myocardial perfusion (subendocardial viability ratio [SEVR]) by pulse wave analysis and endothelial function (reactive hyperemia index [RHI]) by peripheral arterial tonometry. Total and ionized serum calcium were acutely increased by 0.10 ± 0.07 and 0.06 ± 0.03 mmol/L, respectively, 3 hours after calcium citrate administration (p < 0.0001 for both comparisons). Following administration of calcium citrate there was a fall in AIx from a median of 29.7% (23.8% to 34.0%) to 26.4% (22.7% to 34.0%, p = 0.03) and an increase in SEVR from 163% (148% to 174%) to 170% (149% to 185%, p = 0.007). PWV and RHI were not significantly altered. The change in total calcium was negatively correlated with the change in AIx (r = -0.48, p = 0.02). In summary, the acute increase in serum calcium following calcium supplement administration is associated with reduced arterial wave reflection and a marker of increased myocardial perfusion. If maintained long-term, these changes would be expected to reduce cardiovascular risk. Acute serum calcium-mediated changes in these parameters of cardiovascular function are unlikely to underlie an association between calcium supplementation and cardiovascular events.

[Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?]. / Calciumsuppletie bij patiënten met maagzuurremmers: calciumcitraat of calciumcarbonaat?

Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate absorption. No convincing scientific evidence supporting the advice to prescribe calcium citrate instead of calcium carbonate to patients who also take antacids is available, and therefore deserves further investigation. On the contrary, the fact that calcium carbonate does not need acid in order to be absorbed, has also not been proven. In clinical practise, it appears important that calcium is taken with meals in order to improve its absorption.

Calcium supplements lower bone resorption after renal transplant.

AIM: Bone loss in renal transplant (RT) patients is a problem that begins during end-stage kidney disease and persists after transplantation. Suppression of parathyroid hormone (PTH) may decrease bone loss and improve fracture rate. METHODS: A single-group prospective intervention study involving 30 patients was performed at a large RT unit. Investigations included dual-emission X-ray absorptiometry scan, vertebral X-ray, calcium absorption test, 24-h urinary calcium and serum measurements of total and ionized calcium, PTH, C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, 25 hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D3. Patients were given 500 mg elemental calcium daily for seven d, and serum measurements were repeated. RESULTS: Two-tailed Wilcoxon rank-sum test showed significant decreases in PTH (p<0.01) and CTX (p<0.01) after calcium load. Dietary calcium, mean calcium absorption, and urinary calcium excretion were below desirable levels. Mean 25 hydroxyvitamin D (25(OH)D) was low, but levels of 1,25-dihydroxyvitamin D3 were normal. Calcium absorption significantly correlated with change in PTH (p<0.001), baseline 25(OH)D (p<0.001), and mycophenolate dose (p=0.024). CONCLUSIONS: Calcium malabsorption is prevalent in RT recipients, contributing to bone destruction and compounded by poor dietary intake and low 25(OH)D. Calcium supplementation appears to help overcome this deficiency and acutely suppress PTH. Calcium may be an effective and inexpensive therapy for bone loss in RT recipients.

Intravenous ibandronate or sodium-fluoride--a 3.5 years study on bone density and fractures in Crohn's disease patients with osteoporosis.

BACKGROUND AND AIM: Osteoporosis commonly afflicts Crohn's disease (CD) patients. Management remains unclear, with limited results for intravenous (i.v.) bisphosphonates and a follow-up longer than one year. Intravenous bisphosphonates bypass gastrointestinal-tract irritation offering an interesting alternative suitable for CD patients. We tested the long-term efficacy and safety of colecalciferol and calcium with sodium-fluoride or i.v. ibandronate for osteoporosis in CD. METHODS: 66 CD patients with lumbar osteoporosis (T-score<-2.5) were randomized to receive colecalciferol (1000 IU), calcium-citrate (800 mg) and intermittent sustained-release sodium-fluoride (50 mg) [groupA, n=33] or i.v. ibandronate (1 mg/3-monthly) [groupB, n=33]. Dual-energy X-ray absorptiometry of the lumbar-spine and right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading and quantitative morphometry of X-rays. RESULTS: 55 (83.3%) patients completed at least the 1st year available for intention-to-treat (ITT) analysis, 42 (63.6%) completed the 2nd and 35 (53.0%) the 3rd year available for per-protocol analysis. Lumbar T-score increased by +0.23±0.43 (95%CI: 0.057-0.407, p<0.05), +0.71±1.05 (95%CI: 0.193-1.232, p<0.001) and +0.73±0.82 (95%CI: 0.340-1.336, p<0.001) (group A), and +0.28±0.41 (95%CI: 0.132-0.459, p<0.05), +0.43±0.55 (95%CI: 0.184-0.671, p<0.01) and +0.51±0.74 (95%CI: 0.145-0.882, p<0.001) (group B) during 1.0, 2.25 and 3.5 years follow-up time. In 2.71 years of follow-up, with the ITT analysis, the lumbar T-score increased by +0.66±0.97 (group A, p<0.001) and +0.46±0.67 (group B, p<0.001). One vertebral fracture with sodium-fluoride was not enough to detect differences between groups and the study was not powered for this. Study medication was well-tolerated and safe. CONCLUSIONS: Sodium-fluoride and i.v. ibandronate improved osteoporosis. Keeping in mind bisphosphonates as a standard of osteoporosis care that reduce fracture-rate, data we do not have for sodium-fluoride, CD patients with osteoporosis can be treated safely with i.v. ibandronate.