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Objective. Corticosteroids are widely prescribed, although treatment‐related side‐effects are common. Of these adverse events (AEs), osteoporosis is considered the most serious. Currently, oral bisphosphonates are the standard treatment for corticosteroid‐induced osteoporosis (CIO). However, intermittent intravenous (i.v.) therapy may have advantages, including lack of gastrointestinal AEs, improved bioavailability and increased compliance. This study investigated the efficacy and safety of 3‐monthly i.v. ibandronate bolus injections in patients with established CIO. The results from a planned 2‐yr interim analysis are reported.Method. In this controlled, prospective, open‐label, parallel‐group study, 104 patients (49 men and 55 women) with established CIO (mean T‐score <−2.5 s.d. at the lumbar spine (L2–L4) received daily calcium (500 mg) plus either 3‐monthly i.v. ibandronate (2 mg) bolus injections or oral daily alfacalcidol (1 µg). The primary end‐point was bone mineral density (BMD) change at the lumbar spine, femoral neck and calcaneus after 24 months.Results. Compared with oral daily alfacalcidol, i.v. ibandronate produced significantly superior gains in mean (±s.d.) BMD at the lumbar spine (2.2±3.1 vs11.9±7.4%; P<0.001), femoral neck (1.3±1.8 vs4.7±4.0%; P<0.001) and calcaneus (7.6±3.8 vs15.5±10.7%; P<0.0001) after 2 yr. Consistent with these BMD gains and, although the study was not powered for fractures, a trend towards a reduction in vertebral fractures and greater back pain relief was seen in the ibandronate group. The overall incidence of AEs was similar in the two treatment arms.Conclusions. Three‐monthly i.v. ibandronate bolus injections are significantly superior to alfacalcidol in the treatment of CIO. These data confirm the potential of ibandronate for the treatment of osteoporosis associated with corticosteroid use. The ease of administration, lack of AEs and good compliance associated with intermittent i.v. ibandronate make it a potentially valuable alternative to oral bisphosphonate therapy for the treatment of CIO.

Die Supplementation mit Vitamin D und Kalzium wurde bislang bevorzugt in der Therapie der Glucocorticoid-induzierten Osteoporose (GIOP) eingesetzt. Ziel unserer Studie war es, die Effektivität des D-Hormons Alfacalcidol im Vergleich zu Vitamin D bei Patienten mit manifester GIOP mit und ohne vertebralen Frakturen zu untersuchen. Patienten, die unter Langzeit-Corticoid-Therapie standen, wurden entweder mit 1μg Alfacalcidol plus 500mg Kalzium täglich (Gruppe A, N=43) oder 1000I.E. Vitamin D3plus 500mg Kalzium pro Tag (Gruppe B, N=42) therapiert. Die zwei Gruppen unterschieden sich nicht hinsichtlich soziodemographischer Parameter wie Alter, Geschlecht und Begleiterkrankungen, sowie der initialen Knochendichte (Messwerte an der Lendenwirbelsäule (LWS) und am Schenkelhals: mittlerer T-Score –3,28 und 3,25 resp.) und der Anzahl vorliegender vertebraler und peripherer Frakturen.¶ Während der dreijährigen Therapie verzeichneten wir einen signifikanten Anstieg der Knochendichte an der LWS in der Gruppe A (+2,0%, p<0,0001), in Gruppe B konnten keine signifikanten Knochendichteerhöhungen sowohl an der LWS als auch am Schenkelhals registriert werden. Im dreijährigen Behandlungszeitraum traten 12 neue vertebrale Frakturen bei 10 Patienten in der Gruppe A und 21 bei 17 Patienten in der Gruppe B auf (ns). In Übereinstimmung damit konnte eine signifikante Abnahme der Rückenschmerzen in der Gruppe A festgestellt werden (p<0,0001), währenddessen diesbezüglich keine Veränderung der Symptomatik in der Gruppe B auftrat.¶ Wir schlussfolgern, dass die Therapie mit Alfacalcidol der Behandlung mit Vitamin D bei der Therapie der Glucocorticoid-induzierten Osteoporose überlegen ist. Calcium/vitamin D supplementation is generally used as a first step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of this trial was to compare the efficacy of the D-hormone alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures.¶ Patients on long-term glucocorticoid-therapy were treated either with 1μg alfacalcidol plus 5000mg calcium (group A: n=43) or with 1000 IU vitamin D plus 500mg calcium (group B: n=42). The two groups were not different in respect to initial characteristics such as age, sex distribution, concomittant diseases, bone mineral density (mean T-score values at lumbar spine and femoral neck: –3.29 and –3.25 resp.), and in the number of prevalent vertebral and non-vertebral fractures.¶ During the 3 years of treatment we found a significant increase in lumbar spine density in group A (+2.0%, p<0.0001), while no significant changes could be documented in group B at both measuring sites. After 3 years 12 new vertebral fractures had occurred in 10 patients of group A and 21 in 17 patients in group B (ns). Correspondingly we registered a significant decrease of back pain only in group A (p<0.0001).¶ We conclude that alfacalcidol treatment in superior to plain vitamin D in GIOP.

Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1α) compared with the native vitamin D3in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 μg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D3plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score −3.28 and −3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1α (+2.0%, P< 0.0001) and no significant changes at the femoral neck. In the D3group, there were no significant changes at both sites. At the end of the study, 12 new vertebral fractures had occurred in 10 patients of the group 1α and 21 in 17 patients of the D3group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P< 0.0001) whereas no change was seen in the vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.

Paradoxical embolism is well-known in theory but rarely encountered in clinical practice. The typical pathophysiological background is the coincidence of venous thrombosis, elevated right atrial pressure, and a consecutive right-to-left shunting via a patent foramen ovale or an atrial septal defect. We report on a 65-year-old man, who was admitted for acute pain and palor of the left lower leg accompanied by severe dyspnea. On admittance, the left forefoot was pale, pulseless, and cold. The patient showed tachypnea and tachycardia while having a normal blood pressure. The ECG showed an incomplete right bundle branch block and an SIQIII-orientation. Embolic occlusion of the right common femoral artery was proven by immediate angiography. The embolus was removed surgically. A scintigraphy of the lungrevealed multiple bilateral emboli. Phlebography showed right lower leg thrombosis. Under the hypothesis of paradoxical embolism a transesophageal echocardiography was performed, which led to the diagnosis of a patent foramen ovale. The patient presented here represents a characteristical case of a paradoxical embolism via a patent foramen ovale. A venous thrombosis led to a pulmonary embolism with the consequence of elevated right atrial pressure, which resulted in right-to-left shunting and transit of thrombotic material into the systemic circulation with peripheral embolisation. This elucidates the important role of transesophageal echocardiography in patients with arterial emboli. Paradoxe Embolien sind in der Theorie gut bekannt, in der Praxis aber recht selten. Pathophysiologisch liegt typischerweise die Konstellation aus venöser Thrombose, erhöhtem rechtsatrialen Druck und konsekutivem Rechts-Links-Shunt über ein offenes Foramen ovale oder einen Vorhofseptumdefekt zugrunde. Wir berichten über einen 65jährigen Patienten, der wegen eines akuten Schmerzereignisses mit Abblassen der Hautfarbe des linken Unterschenkels aufgenommen wurde. Zugleich hatte heftige Luftnot eingesetzt. Bei Aufnahme war der linke Vorfuß blaß, kalt und pulslos. Außerdem war der Patient tachypnoisch, tachykard und normoton. Im EKG Rechtsverspätung und SIQIII-Typ. Die Angiographie zeigte einen Verschluß der A. femoralis communis. Zunächst erfolgte die Embolektomie, anschließend wurden in einem Lungenszintigramm multiple Lungenembolien beidseits festgestellt. Phlebographisch wurde eine Unterschenkelvenenthrombose rechts diagnostiziert. Unter dem Verdacht auf eine paradoxe Embolie wurde eine transösophageale Echokardiographie (TEE) durchgeführt. Diese ergab ein offenes Foramen ovale. Der vorliegende Fall stellt beispielhaft den Ablauf einer paradoxen Embolie bei patentem Foramen ovale dar. Eine Phlebothrombose führt zur Lungenembolie, in deren Rahmen der rechtsatriale Druck ansteigt und Thrombenmaterial in den Systemkreislauf gelangen kann, wo es arteriell embolisiert. Die Bedeutung der TEE bei arteriellen Embolien wird deutlich.

Summary In 75 operatively proved cases of primary hyperparathyroidism (PH) mean systolic and diastolic blood pressure (BP) values were significantly higher pre- than postoperatively. There were 27 patients (36%) who showed hypertension before operation (systolic BP?150 mm Hg, mean 169±20 mm Hg). In 20 of these the hypertension was reversible after successful treatment of PH, in seven cases elevated values persisted. The mean age of patients with persisting hypertension was significantly higher than the group with normalization of BP after operation (P<0.01). As far as clinical presentation of PH was concerned it were those cases with hypercalcaemic syndrome and with accidentally discovered hypercalcaemia who most often showed hypertension. In cases with recurrent urolithiasis and with osteitis fibrosa as leading symptoms there was no significant increase of hypertension as compared to the whole group. Because of the relatively high incidence of hypertension in PH this possibility should be taken into consideration in each diagnostic clarification of hypertensive patients.

Summary 40 out of 98 patients on chronic haemodialysis show an obviously lowered bone mineral content of the radius (mean -20.4%), 51 patients attain values in the normal range (mean -1%) and 7 subjects slightly increased values (mean +10.9%). A bone mineral loss of 2.5% could be found after long-term observations of this parameter between 6 to 30 months (mean observation period: 15 months). In general a progressive loss of the bone mineral content may be noticed with an increased duration of haemodialysis. This tendency is more distinct after the 40th year of life because of the simultaneous age-depending physiological decrease of bone mass. Abruptly occurring mineral losses of the skeleton may be due to a high incretion of parathyroid hormone and possibly require subtotal parathyroidectomy.

The cytogenesis of giant osteoclasts in Paget's disease of bone was studied by means of electron microscopy. 26 iliac crest biopsies were made and divided for light and electron microscopic investigation. A special procedure was used for electron microscopic preparation of bone without previous decalcification.

We investigated how calcium channel blocking agents modify the known decrease of QT time with increasing heart rate and calcium level. Furthermore, we examined how the influence of calcium channel blocking agents is modulated by atrial stimulation. To answer these questions, we measured the QT time both at a spontaneous heart rate and during atrial stimulation with 90 and 110 beats/min before and after intravenous administration of 5 mg verapamil in 23 patients with primary hyperparathyroidism, pre- and postoperatively. Atrial stimulation increased the frequency-related standard values of QT time. The spontaneous heart rate (HR) was influenced by neither the calcium level nor verapamil. The statistically significant correlations QT vs. HR and QT vs. Ca were reduced by verapamil, which indicated its influence. However, this effect did not achieve statistical significance.

Abstract:: Recent experience from different groups suggests that low fluoride doses resulting in moderate increases in bone mineral density (BMD) may be advantageous in terms of fracture-reducing potency. In a randomized prospective 3-year study we examined the therapeutic efficacy of different dosages of monofluorophosphate (MFP) plus calcium in comparison with calcium alone in 134 women with established postmenopausal osteoporosis (mean age 64.0 years, average vertebral fractures per patient 3.6). Group A received 1000 mg calcium/day and a low-dose intermittent MFP regimen (3 months on, 1 month off) corresponding to an average daily fluoride ion dose of 11.2 mg. Group B received 1000 mg calcium/day plus continuous MFP corresponding to 20 mg fluoride ions per day. Group C was treated with 1000 mg calcium alone throughout the study period. Bone density was measured with dual-energy X-ray absorptiometry at L2–4 and three proximal femur areas and with single photon absorptiometry at two radius sites. New vertebral fractures were identified from annual lateral radiographs of the spine. A significant reduction in subjective complaints as measured by a combined pain–mobility score (CPMS) was found in both fluoride groups in comparison with the calcium monotherapy group. Group A showed increases in BMD at all six measuring sites, reaching +12.6% at the spine after 3 years. In group B we found significant increases at the spine, Ward’s triangle and distal radius, but slight decreases at the femoral neck and radius shaft. For the spine the average change amounted to +19.5% after 3 years. In group C losses of BMD were observed at all six sites, with an average loss of 1.6% for the spine at the end of the study. The incidence of new vertebral fractures per 100 patient-years was 8.6, 17.0 and 31.6 in groups A, B and C, respectively. In conclusion, both calcium–MFP regimens resulted in significantly lower vertebral fracture rates than calcium monotherapy. However, the low intermittent MFP regimen, leading to a mean annual increase in spinal BMD of only 4.2%, showed a clear trend to greater effectiveness in reducing vertebral fracture than the higher fluoride dosage that was followed by an average spinal BMD increase of 6.5% per year. Furthermore the rate of fluoride-specific side effects (lower-extremity pain syndrome) was 50% lower in patients receiving the lower fluoride dosage.

It has been investigated whether calcium- and verapamil-dependent sensitivities of carotis baroreceptors also exist in man. To answer this question, we pre- and postoperatively measured changes in heart rate during carotid sinus stimulation before and after intravenous administration of 5 mg verapamil in 23 patients with primary hyperparathyroidism. Findings during hypercalcemia were as expected: a more pronounced reduction of heart rate at comparatively low calcium levels. During normocalcemia, we found an opposite effect: a more pronounced reduction at relatively high calcium levels, which was statistically significant. This fact could be explained according to our interpretation. In previous reports, local effects on baroreceptors were examined, whereas we measured the combined effect of several calcium actions. As expected, verapamil attenuated the decrease in heart rate which, however, was not statistically significant.