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Hintergrund Die mannliche Osteoporose zahlt mit uber 1 Mio. Betroffener in Deutschland nicht zu den seltenen Erkrankungen. Osteoporotische Frakturen haben bei Mannern eine hohere Mortalitat als bei Frauen, werden aber selten abgeklart oder einer spezifischen Therapie zugefuhrt.

Eine ungenugende Kalzium(Ca)-Zufuhr fuhrt zu Knochenabbau und ist damit ein Osteoporoserisikofaktor. Bei Ca-Mangel wird ein normaler Serum-Ca-Spiegel uber vermehrte Parathormonsekretion auf Kosten des Skeletts aufrechterhalten, d. h., es entwickelt sich ein sekundarer Hyperparathyreoidismus. Vitamin D (Vit. D) begunstigt die intestinale Kalziumresorption sowie die Mineralisation der Knochenmatrix und hemmt gleichzeitig die Nebenschilddrusen. Von daher werden Ca-/Vit.-D-Supplemente generell zu Pravention und Basistherapie der Osteoporose empfohlen. Fur die Dosierung dieser Supplemente mussen die individuelle alimentare Ca-Zufuhr und die Vit.-D-Eigensynthese bei Sonnenexposition berucksichtigt werden. Zu beachten ist, dass mit steigendem Lebensalter Ca-Zufuhr, -resorption und Sonnenexposition abnehmen. Anzustreben sind eine Ca-Zufuhr von 1000–1500 mg und Vit.-D-Einnahme von 800–2000 IE/Tag bzw. Serumkonzentrationswerte von 25-Hydroxy-Vitamin-D von 30–50 ng/ml. Unter diesen Dosierungen treten Hyperkalzamie und Hyperkalzurie praktisch nicht sowie Nierensteine sehr selten auf. Mitteilungen in den letzten Jahren uber ein erhohtes kardiovaskulares Risiko durch langzeitige Kalziumsubstitution oder auch die kombinierte Einnahme von Ca/Vit.-D haben zu einer erheblichen Reduktion der Verordnung der entsprechenden Praparate gefuhrt. Andererseits gibt es jedoch Hinweise, dass optimale Vit.-D-Werte kardioprotektiv sind und neuere Studien, die ein erhohtes kardiovaskulares Risiko nicht bestatigen bzw. eine reduzierte Mortalitat bei Ca/Vit.-D-Substitution beschreiben. Bis zur endgultigen Klarung dieser diskrepanten Befunde wird die regelmasige moderate Ca/Vit.-D-Substitution im oben genannten Dosisbereich empfohlen.

ZusammenfassungEtwa sechs Prozent der über 50-jährigen Männer sind in Deutschland von Osteoporose betroffen. Obgleich bereits eine breite Palette an Medikamenten zur Behandlung der männlichen Osteoporose zur Verfügung steht, und Männer mit osteoporotischen Frakturen eine deutlich höhere Mortalität als Frauen mit Frakturen haben, werden Männer seltener behandelt. Nach einer Hüftfraktur werden etwa zwei Drittel aller Frauen mit einem osteoporosespezifischen Medikament behandelt, bei Männern ist es aber nur die Hälfte. Bei Männern stehen in 50–60 % der Fälle sekundäre Osteoporosen im Vordergrund, bei postmenopausalen Frauen hingegen nur bei 30 %. Die häufigsten Risikofaktoren bei der männlichen Osteoporose sind Nikotinkonsum, systemische Glukokortikoide, Alkoholkonsum, chronisch obstruktive Atemwegserkrankungen und der Hypogonadismus. Screening hinsichtlich des Vorliegens von Risikofaktoren ist daher bei Männern zur Früh-erkennung der Osteoporose unerlässlich. Im positiven Falle ist eine systematische osteologische Abklärung inklusive Knochendichtemessung, Bildgebung der Wirbelsäule und Labordiagnostik erforderlich. Prävention muss bereits im Kindesund Jugendalter erfolgen durch körperliche Aktivität, eiweiß- und kalziumreiche Ernährung kombiniert mit adäquater Vitamin-D-Versorgung. Bereits bei Diagnosestellung von Erkrankungen, die mit der Entwicklung einer Osteoporose verbunden sein können, ist osteologische Diagnostik erforderlich. Nur so kann der Entwicklung einer Osteoporose frühzeitig begegnet werden.

Summary Introduction: Optimal duration of bisphosphonate (BP) therapy has not been defined. A recent FDA publication suggests periodically re-evaluating patients on BP. Those with low risk may discontinue BP after 3–5 years, those still at high risk may benefit from ongoing BP. Patients and methods: We compared continued BP therapy plus plain vitamin D to BP plus alfacalcidol in patients still at a significantly increased fracture risk after an average of 4.3 years of BP plus plain vitamin D use over two more years. The study was based on retrospective chart analysis and followed 214 patients (167 female, 47 male). Among these 145 continued alendronate (ALN) and 69 risedronate (RIS). In addition, group A (n = 106) received 800 IU/d plain vitamin D plus 1200 mg/d calcium as before, while patients in group B (n = 108) were switched from plain vitamin D to 1 μg/d alfacalcidol plus 500 mg/d calcium. The respective proportions of males and females and patients with ALN or RIS intake did not differ between group A and B. BMD was measured at 0, 12 and 24 months at lumbar spine (LS) and femoral neck (FN) by DXA. Lateral spine morphometry assessed prevalent and incident vertebral fractures. Recorded were the number of falls and fallers 2 years before and during the trial, back pain (VAS 0–10), adverse events (AE) and prevalent and incident non-vertebral fractures. We also conducted subgroup analyses in four groups – female, male, ALN, RIS on all endpoints. Results: BMD at LS did not change significantly over two years with +1.1 % in group A, but increased significantly with BP plus alfa-calcidol by + 5.5 % (B vs. A p < 0.01). At the FN site the respective changes were +0.6 % and +3.4 % (p < 0.01). The average number of falls per patient-year was reduced by 12 % in A (ns) and by 44 % in B (p < 0.03). There was a significant decrease in average back pain score with BP plus alfa calcidol vs. BP plus plain vitamin D after two years (p < 0.02). The number of patients with new vertebral fractures did not significantly differ between A and B. There were however significantly less non-vertebral fractures with alfacalcidol (p < 0.05). The above was found significant in all subgroups for nearly all endpoints. The number of adverse events (AE) did not differ between groups. No serious AE were observed. Discussion: The data show that in male and female osteoporosis patients still at risk after 4.3 years on oral BP a continuation of BP plus alfacalcidol is superior to ongoing therapy with BP plus plain vitamin D.

SummaryOsteoporosis in men is increasingly recognized as an important public health problem but affected patients are still under-diagnosed and -treated. As in women the diagnostic and therapeutic strategy has to be adapted to the individual case. In the practical management it is very important to detect possible causes of secondary osteoporosis, to explain the possibilities of basic therapy counteracting individual risk factors and communicate that osteoporosis is a chronic disease and adherence to a long-term treatment is crucial. In established severe osteoporosis a careful analgesic therapy is important to avoid further bone loss related to immobility. In elderly men with increased risk of falling insufficient Vitamin D supply or impaired activation of Vitamin D due to renal insufficiency must be taken into consideration. Specific medications available today for the treatment of male osteoporosis comprise among antiresorptive drugs the bis phosphonates alendronate, risedronate and zoledronic acid. Denosumab, the first biological therapy is approved for men with androgen deprivation therapy for prostate cancer. An important advantage of this potent antiresorptive drug is the increased adherence due to the comfortable application by sixmonthly subcutaneous injections. Study results from the 2-year multi-center randomized controlled ADAMO-Study will very soon allow the use of denosumab in all types of male osteoporosis. Teriparatide, the 34 N-terminal amino acid sequence of parathyroid hormone was approved for men with osteoporosis as an anabolic agent based on proven efficacy by different studies. Among drugs with other modes of action the D-hormone pro-drug alfacalcidol can be used in men alone or in combination with the advantage of pleiotropic effects on calcium absorption, parathyroids, bone and muscle. Recently also Strontium-ranelate was approved for male patients with the limitation to exclude men with clinical relevant cardiovascular risk factors. In general the possibilities to treat male osteoporosis have considerably improved during recent years. Today there is a choice of a spectrum of drugs from mild to strong potency with different modes of action on bone turnover to design strategies for individual male patients.

Due to pleiotropic-synergistic actions on bone, muscle, gut, brain and different other non-skeletal tissues, alfacalcidol is an interesting drug for treating osteoporosis. In studies on glucocorticoid-induced osteoporosis, men have always been treated with calcitriol or this active D-hormone prodrug, but there is no study of male patients only in the literature. The AIM-Trial (Alfacalcidol In Men) is an extension of the control group (n = 158) of our former risedronate study in male osteoporosis (Ringe et al. in Rheumatol Int 29:311-315, 2009). In that study, we treated daily those controls with prevalent vertebral fractures with 1 μg alfacalcidol + 500 mg calcium (group A) and those without prevalent vertebral fractures with 1,000 IU plain vitamin D (Vit. D) + 1,000 mg calcium (group B). Subsequently, we added an additional 56 pairs of patients to these two groups: 28 with and 28 without prevalent vertebral fractures, reaching a total of 214 cases. That means with this design, we are comparing two groups with a different risk at onset. Due to the prevalent vertebral fractures and lower average bone mineral density (BMD) values, there was a higher risk of incident fractures in group A. After 2 years, we found significantly higher increases in lumbar spine BMD (+3.2 vs. +0.8 %) and total hip BMD (+1.9 vs. -0.9 %) in group A and B, respectively. Eighteen incident falls were recorded in the alfacalcidol group and 38 in the group treated with Vit. D (p = 0.041). There were significantly lower rates of patients with new vertebral and non-vertebral fractures in group A than in group B. Back pain was significantly reduced only with alfacalcidol. Concerning the incidence of new non-vertebral fractures, we found that there was a relation to renal function in the two groups. The advantage for alfacalcidol was mainly due to a higher non-vertebral fracture-reducing potency in patients with a creatinine clearance (CrCl) below 60 ml/min (p = 0.0019). There were no serious adverse events (SAE), and the numbers of mild-to-moderate adverse events (AE) were not different between groups. Despite the higher initial fracture risk in the alfacalcidol group, 2-year treatment with this active D-hormone prodrug showed a higher therapeutic efficacy in terms of BMD, falls and fractures. One important advantage of alfacalcidol may be that it is effective even in patients with mild-to-moderate renal insufficiency.

ZusammenfassungEine langjährige orale Bisphosphonat (BP)– Behandlung der Osteoporose kann durch übermäßige Suppression des Knochenumbaues negative Effekte auf die Knochenqualität haben. Es gibt bislang keine verbindlichen Empfehlungen zur Anwendungsdauer der BP, aber eine Therapieunterbrechung nach etwa fünf Jahren wird heute überwiegend angeraten. Bezüglich anschließenden Folgebehandlung gibt es allerdings auch kaum publizierte wissenschaftliche Daten. Wir haben in einer zweijährigen Studie an 85 Frauen mit postmenopausaler Osteoporose nach einer mittleren BP-Einnahmedauer von 4,2 Jahren zwei verschiedene Folge behandlungen vergleichend untersucht: Gruppe A (n = 42) erhielt 800 IE natürliches Vitamin D + 1200 mg Kalzium pro Tag, Gruppe B (n = 43) 1 µg Alfacalcidol + 500 mg Kalzium pro Tag. Primärer Endpunkt war die Änderung der Knochenmineraldichte (BMD) nach 12 und 24 Monaten. Weitere Endpunkte waren neu auftretende Stürze und Frakturen, Rückenschmerz (VAS 0–10) und unerwünschte Therapieeffekte. Zwischen den beiden Gruppen bestanden keine Unterschiede in den Ausgangscharakteristika Alter, Body-Mass-Index, Größenverlust, BMD, Rückenschmerz-Score und der Anzahl vorbestehender Stürze und Frakturen. In Gruppe A änderten sich die BMD-Werte an der LWS nicht signifikant während der zwei Jahre Follow-up nach Absetzen der BPEinnahme. Dagegen zeigte sich in Gruppe B für die LWS ein signifikanter Anstieg von 2,1 % (B vs. A p < 0,01). An den zwei Femurmessorten fanden wir leichte Abnahmen in der Vitamin-D-Gruppe und einen signifikanten Anstieg unter Alfacalcidol. Die mittlere Anzahl von Stürzen pro Patient blieb unverändert in Gruppe A und nahm signifikant ab in Gruppe B (p < 0,05). Die Anzahl der Patienten mit neuen Wirbelfrakturen unterschied sich nach zwei Jahren nicht zwischen beiden Therapiegruppen, während die Inzidenz von nichtvertebralen Frakturen in der Alfacalcidol-Gruppe signifikant niedriger ausfiel (p < 0,05). Des Weiteren fand sich eine signifikant stärkere Verminderung der Rückenschmerzen bei den Patienten unter Alfacalcidol- Behandlung. Bezüglich der Häufigkeit unerwünschter Wirkungen fand sich kein Unterschied zwischen den beiden Gruppen. Die Ergebnisse zeigen, dass eine Therapieumstellung nach langzeitiger BP-Anwendung bei postmenopausaler Osteoporose auf Alfacalcidol der Nachbehandlung mit natürlichem Vitamin D überlegen ist.

ZusammenfassungDer Morbus Paget des Knochens weist eine Reihe von epidemiologischen Besonderheiten auf, die bis heute viele Fragen aufwirft. Das Auftreten des Erkrankungsbildes vor dem 40. Lebensjahr ist sehr selten, erreicht aber in der Altersgruppe > 80 Jahre in einigen Populationen Prävalenzraten von 6,9 bis 10 %. Auffällig ist zudem eine sehr ausgeprägte Variation der Prävalenz mit besonders hohen Raten in bestimmten geografischen Regionen Nordenglands, Süditaliens und bestimmten Bezirken Spaniens. Demgegenüber steht das extrem seltene Auftreten in Skandinavien und Afrika. Aktuelle Untersuchungen weisen in einigen Regionen auf eine rückläufige Inzidenz, Prävalenz, Morbidität und Mortalität der Erkrankung hin. Neben dem sporadischen Auftreten der Erkrankung werden auch familiäre Häufungen mit früherem Krankheitsbeginn und einem anderen Befallsmuster beobachtet.

This prospective, non-interventional study (OROSANA4001) was conducted at 71 sites throughout Germany. 219 adults with chronic pain due to osteoporosis and a pain intensity ≥6 on a numerical rating scale (NRS 0-10) were documented. Pain relief was rated by the patients on a scale from 0% (no relief) to 100% (complete relief) and the interference of pain with general activity was assessed on a scale from 0 to 10. Furthermore, satisfaction with pain therapy (by patient and physician) and patient's capability of physical therapy were evaluated. Tolerability was assessed by documentation of adverse events and study discontinuation. Treatment with oral osmotic hydromorphone decreased all pain intensity ratings significantly from baseline to the last assessment (p

Zusammenfassung Ziel: Die prospektive, nichtinterventionelle OLYMP-Studie untersucht die Wirkung von Strontiumranelat (SR) bei postmenopausaler Osteoporose (PMO) hinsichtlich Schmerzen und Lebensqualität unter Praxisbedingungen. Design: 3383 Patienten mit PMO wurden von 1131 niedergelassenen Ärzten in Deutschland mit SR 2 g einmal täglich oral über drei Monate therapiert. Lebensqualität (QoL), Schmerzen, Komedikation, Frakturen, Knochendichte, Verträglichkeit und Compliance wurden deskriptiv an 3164 Patienten (ITT) analysiert. 39,1 % der Patienten waren mit Bisphosphonaten (BP) vorbehandelt, 26 % der Patienten waren > 75 Jahre alt. Ergebnisse: Nach drei Monaten SR verbesserten sich die Schmerzen um 32,3 % (Patienten mit BP-Vorbehandlung: 28,3 %, Patienten ohne Vorbehandlung: 35,6 %, Patienten > 75 Jahre: 28,6 %) und die QoL um 27,5 % (Patienten mit BP-Vorbehandlung: 24,5 %, Patienten ohne Vorbehandlung: 30,2 %, Patienten > 75 Jahre: 24,4 %). SR wurde bei 93 % der Patienten als sehr gut bzw. gut bewertet und bei 93,2 % der Patienten nach drei Monaten fortgesetzt. UAWs traten bei 2,4 % der Patienten auf. Zusammenfassung: OLYMP bestätigt unter Praxisbedingungen die gute Wirksamkeit und Verträglichkeit von SR bei PMO unabhängig von Alter und BP-Vorbehandlung mit einer raschen Schmerzreduktion und Verbesserung der QoL.

A 72-year-old man had had recurrent fever of undetermined cause, for which he had repeated periods in hospital. There were no specific organ-related symptoms. Conventional radiology of the vertebrae, tomography, CT scan and CT-guided needle biopsy finally revealed the presence of staphylococcal spondylitis of thoracic vertebrae 11 and 12 with bilateral paravertebral abscesses. Particularly valuable diagnostically was the CT scan with demonstration of bony destruction in the axial plane and of the paravertebral soft-tissue changes, as well as the use of CT-assisted puncture of the abscess. Asymptomatic spondylitis should be thought of as a possible cause of pyrexia of unknown origin.

In einer prospektiven Studie wurde bei einer Gruppe konsekutiv zugewiesener Manner (n = 321, Alter zwischen 16 und 86 Jahren) durch ein standardisiertes klinisches Untersuchungsprogramm in 254 Fallen (79 %) eine Osteoporose diagnostiziert. Das Programm umfaste sorgfaltige Anamneseerhebung und korperliche Untersuchung, klinischchemische Untersuchungen, Rontgenaufnahme des Skeletts und Osteodensitometrie. Bei daraus resultierendem Verdacht auf bestimmte Grundkrankheiten oder Risikofaktoren wurde das Programm gezielt erweitert. 39 % der Manner (n = 98) wiesen eine praklinische Osteoporose auf, 61 % (n = 156) eine manifeste Erkrankung mit einer oder mehreren Wirbelkorperfrakturen. Bezuglich der Knochendichtemeswerte waren praklinische und manifeste Falle nicht signifikant verschieden. Bei 76 der 254 Patienten (30 %) fehlten jegliche pathogenetische Faktoren, daher wurde die Osteoporose als idiopathisch klassifiziert (mittleres Alter 51 Jahre), bei 16 alteren Patienten als senile Osteoporose (mittleres Alter 78 Jahre). In den ubrigen 162 Fallen lagen 286 Risikofaktoren zugrunde, die 24 verschiedenen Kategorien zuzuordnen waren. Je nach Dauer, Intensitat und Kombination dieser Risikofaktoren wurden die Krankheitsfalle als primare Osteoporosen mit geringen Risikofaktoren, monoatiologische oder polyatiologische sekundare Osteoporosen eingestuft (mittleres Alter dieser Gruppen 51, 56 und 52 Jahre). Die wichtigsten nachgewiesenen Risikofaktoren waren in abnehmender Haufigkeit: Glucocorticoidtherapie, Alkoholkonsum, Rauchen, Hypogonadismus, Hypercalcurie, Hepatopathie, Morbus Crohn, Calciummangelernahrung, Hyperthyreose, korperliche Inaktivitat, Magenoperation und Plasmozytom. - Der Nachweis eines bedeutsamen Risikofaktors und besonders der Kombination mehrerer Risikofaktoren sollte als Indikation fur eine vorsorgliche Knochendichtemessung angesehen werden, um fruh eine Osteoporosetherapie einleiten zu konnen. Bei bereits diagnostizierter Osteoporose ist eine Stadienzuordnung und genaue Risikofaktorenanalyse Voraussetzung fur eine ursachenorientierte Therapie. In a prospective study, 321 consecutive male patients, aged between 16 and 86 years, referred to the Department of Medicine of the Medical Centre at Leverkusen from many parts of Germany over a three-year period with the diagnosis of osteoporosis, underwent a standardized programme of clinical investigation: 254 (79 %) were found to have the condition. The Programme consisted of a detailed history, physical examination, a battery of laboratory tests, X-ray examination of the skeleton and osteodensitometry. Where, as a result, underlying disease or risk factors were suspected, further tests were performed. 98 patients (39 %) were found by densitometric criteria to have preclinical, 156 (61 %) manifest osteoporosis with one or more vertebral body fractures. There was no significant difference regarding bone density between the preclinical and manifest cases. 76 of the 254 (30 %) patients had no detectable pathogenetic factors, i. e. their osteoporosis was classified as idiopathic (mean age 51 years), while as senile osteoporosis in 16 elderly patients (mean age 78 years). The remaining 162 patients had 286 risk factors within 24 different categories. Depending on duration, intensity and combination of these risk factors, the osteoporosis was classified as primary with few risk factors or as secondary osteoporosis of single or multiple aetiology (mean age of these three groups was 51, 56 and 52 years, respectively). The most important demonstrable risk factors were (in decreasing order of frequency) glucocorticoid treatment, alcohol consumption, smoking, hypogonadism, hypercalciuria, liver disease, Crohn's disease, low calcium nutrition, hyperthyroidism, physical inactivity, stomach operation and plasmacytoma. - This study indicates that if there is evidence of significant risk factors detailed bone densitometry should be performed so that any necessary treatment can be initiated early. If there is known osteoporosis, staging and exact analysis of risk factors is a precondition for any cause-oriented treatment.

Average interval from initial symptoms to diagnosis in 47 patients with non-tropical sprue was 8.3 years. Predominantly skeletal symptoms without typical gastro-intestinal symptoms occurred in about one third of cases, probably a reason for the delay in diagnosis. In more than 90% of cases there was the histological picture of osteopathy, osteomalacia with or without secondary hyperparathyroidism being about twice as frequent than osteoporosis. Biochemical and histological findings correlated well. In more than 80% of cases the mean mineral content of the radius bone was reduced by more than 30% of normal, while radiological findings were abnormal in only just half the cases. Even in the absence of diarrhoea, non-tropical sprue should be considered in aetiologically uncertain cases of generalised osteopathy.

Fifty-nine consecutive patients (19 men, 40 women, mean age 60.8 [27-80] years) with primary osteoporosis were studied to see if there was any significant gain in bone mass after treatment with salmon calcitonin. All the patients were given 1 g calcium by mouth every morning. Group 1 (n = 20) received no other specific medication while group 2 (n = 19) were given 100 I.U. calcitonin subcutaneously every second evening and group 3 (n = 20) received the same dose every evening. The pain reported by the patients was subdivided into four severity grades, and analgesic consumption was recorded. In group 1 there was a nonsignificant decrease in pain, but in groups 2 and 3 there was a highly significant diminution in pain (P less than 0.005) and in analgesic intake (P less than 0.01). Measurements of bone density carried out by photon absorption at the end of 12 months showed a 5.5% increase in the distal radius in group 2 (P = 0.0001) and a 7.1% increase in group 3 (P = 0.0001), while in group 1 mineral content had decreased by 4.3% (nonsignificant). These results show that a significant gain in bone mass can be achieved by administration of calcitonin, either daily or on alternate days. The incidence of extravertebral fractures and of new or progressive vertebral deformity tended to be lower in groups 2 and 3 than in group 1.

ZusammenfassungBei Störungen des Phosphatstoffwechsels sind die extremen Normabweichungen der Serumspiegel klinisch meist einfach zu werten. Eine signifikante, persistierende Hypokalzämie, z. B. bei renal-tubulärem Phosphatverlust, führt eindeutig zur Osteomalazie. Die chronische Hyperphosphatämie, z. B. bei dialysepflichtiger Niereninsuffizienz, bedeutet ein hohes Risiko extraossärer Kalzifikationen. Eine stark gesteigerte orale Phosphatzufuhr hat bei wachsenden Ratten negative Effekte auf den Kalzium- und Knochenstoffwechsel und führt zu deutlicher Reduktion der Knochenfestigkeit. Eine nutritiv bedingte Hyperphosphatämie kommt jedoch beim Erwachsenen mit normaler Nierenfunktion praktisch nicht vor, da die renale Phosphateliminations-Kapazität der Nieren sehr hoch ist. Auch ein alimentär bedingt höhergradiger Phosphatmangel ist bei gesunden Erwachsenen bei der üblichen eher phosphatreichen Ernährung selten. Allenfalls bei 5–15 % der älteren Bevölkerung können niedrig normale oder leicht verminderte Serum-Phosphatspiegel gefunden werden. Solange die Serum-Phosphatspiegel über1 mmol/l (= 3,1 mg/dl) liegen, ist im Milieu des Knochengewebes eine ausreichend hohe Konzentration diese Anions für die Mineralisation vorhanden, d. h. eine Mineralisationsstärung tritt noch nicht auf. Wichtig und bislang noch nicht genügend gewürdigt sind jedoch Untersuchungen, die darauf hinweisen, dass die gut gemeinte routinemäßige, langzeitige Substitution mit nichtphosphathaltigen Kalziumsalzen bei älteren Osteoporosepatienten durchaus zu einer relevanten Phosphatinsuffizienz führen kann. Daraus wurde die Empfehlung abgeleitet, älteren Osteoporosepatienten zumindestens einen Teil ihrer Kalziumsupplemente in Form von Kalziumphosphat zu verordnen. Diese Sicht wird durch eine aktuelle Meta-Analyse gestützt. Weitere klinische Forschung bezüglich der Interaktionen von Kalzium und Phosphat in der Ernährung erscheinen jedoch dringend nötig. Möglicherweise ist die viel zitierte Gefahr einer reduzierten Kalziumaufnahme aus dem Darm durch phosphatreiche Kost klinisch weniger relevant als die wenig bekannte umgekehrte Gefahr eines Phosphatmangels durch chronisch hoch dosierte, phosphatfreie Kalziumsupplemente.

While in other chronic diseases combined treatment regimens are the rule there is a lack of reported experience or study data on combining different specific drugs to treat osteoporosis. Significant differences in the mode of action (MOA) of the substances to be combined may be important for achieving optimal therapeutic results. Recognising that today bisphosphonates are the leading therapy for osteoporosis we suggest that the active D-hormone analog alfacalcidol with its completely different mechanisms of action could be an interesting combination to improve the therapeutic outcome of the pure antiresoptive action of bisphosphonates. Alfacalcidol is activated by the enzyme 25-hydroxylase in the liver for systemic and in osteoblasts for local D-hormone actions. It possesses a unique pattern of pleiotropic effects on, e.g. gut, bone, pararthyroids, muscle and brain. Alfacalcidol is superior to plain vitamin D (cholecalciferol) because the final kidney activation of the latter is regulated by a negative feedback mechanism. In vitamin D replete patients or patients with impaired kidney function no increased D-hormone action at the target tissues can be achieved. Animal studies and several trials in humans with alendronate plus calcitriol or alfacalcidol proved that the combination induced significantly higher increases of bone mineral density (BMD) than the respective mono-therapies. The results of the 2-year AAC-trial from our group indicate that the combination alendronate and alfacalcidol is also superior in terms of falls, fractures and back pain. From the review of the literature and the own new results we conclude that this combined therapeutic regimen is a very promising option for treating established osteoporosis and propose a differentiated use of alfacalcidol alone or the combination with alendronate in different stages and clinical situations of osteoporosis.

A combined therapy with the strongly antiresorptive Alendronate and the pleiotropically acting D-hormone analogue Alfacalcidol may have additive effects on bone quality, falls and fracture risk in established osteoporosis. The aim of this study (Alfacalcidol Alendronate Combined-AAC) was to compare the efficacy and safety of a combined parallel therapy with Alendronate and Alfacalcidol to the treatment with either Alendronate in combination with plain vitamin D or Alfacalcidol alone in patients with established postmenopausal or male osteoporosis. Ninety patients were included as matched triplets to receive randomly either 1 microg Alfacalcidol daily + 500 mg calcium (group A, n = 30) or 70 mg Alendronate weekly + 1,000 mg calcium + 1,000 IU vitamin D daily (group B, n = 30) or 1 microg Alfacalcidol daily + 70 mg Alendronate weekly + 500 mg calcium daily (group C, n = 30). Patients were recruited in one centre and were followed up for 24 months. Analysis was intention-to-treat and the primary outcome was lumbar spine and total hip bone mineral density (measured observer blind). BMD was measured at the lumbar spine and at the proximal femur with dual energy X-ray absorptiometry (LUNAR Prodigy, GE, USA) at the beginning and after 12 and 24 months. During the 2-year-study we observed descriptively significant increases at the lumbar spine of 3.0% in group A compared to baseline, of 5.4% in group B and of 9.6% in group C, respectively. The superiority of the Alendronate + Alfacalcidol treatment group over Alfacalcidol alone and over Alendronate + vitamin D was of more than large rele-vance (both tests: MW0.71; CI-LB0.64; P0.001). We also observed median increases of the BMD at the total hip of 1.5% in group A, of 2.4% in group B and of 3.8% in group C, respectively. The superiority of group C over group A and over group B again was relevant and statistically significant in a descriptive sense. After 2 years there was a tendency towards higher rates of vertebral and non-vertebral fractures in group A and B as compared to C. Taking both fracture types together we observed 9, 10 and 2 "osteoporotic fractures" in groups A, B and C, respectively. The comparison of group C with pooled groups A and B and with each single group gave a relevantly lower fracture rate for the combination of Alendronate and Alfacalcidol. Furthermore a lower rate of falls was observed for the combination Alendronate plus Alfacalcidol versus Alendronate + vitamin D, but not versus Alfacalcidol alone. We found 80% of the patients in the Alendronate + Alfacalcidol group free from back pain at month 24, compared to 30% in the Alendronate + vitamin D and 43% in the Alfacalcidol monotherapy group. The superiority is relevant (both tests: MW0.64; CI-LB0.56; P0.003). Pain decrease also occurred more rapidly in the Alendronate + Alfacalcidol group than in the other groups. In general side effects in all groups were mild, and only four cases of moderate hypercalcuria in group A and one in group C were reported, but no case of hypercalcemia was documented. In conclusion, the combination therapy with Alendronate and Alfacalcidol exhibited superiority in terms of BMD, overall fractures, rate of falls and back pain over either Alendronate in combination with plain vitamin D or Alfacalcidol alone. The overall safety profiles of the three treatment regimens were found to be not different in this study.

ZusammenfassungDie Bedeutung der Osteoporose des Mannes nimmt rasant zu. Fast jeder fünfte Osteoporose-Patient in der Praxis ist heute bereits ein Mann. Die Diagnose wird jedoch zu selten gestellt und die wenigen bislang therapierten Fälle werden oft falsch oder inkonsequent behandelt. Als Verdachtsmomente auf das Vorliegen einer Osteoporose sind unklare Rückenbeschwerden, Größenabnahme, Rundrücken, Kalksalzminderung im Röntgenbild und gehäufte Frakturen einzeln genommen unsichere Kriterien. Eine eindeutige Diagnosestellung ist jedoch durch Anamnese und körperliche Untersuchung, Osteodensitometrie und Röntgen der Wirbelsäule sowie ergänzende Laborparameter einfach zu bewerkstelligen. Wie bei der postmenopausalen Osteoporose beinhaltet die Therapiestrategie Basistherapie (insbesondere Calcium/Vitamin D Substitution), Schmerz-therapie und spezifisch medikamentöse Therapie zur Reduktion des Knochenumbaus bzw. Stimulation des Knochen- anbaus. Die spezifische medikamentöse Behandlung ist weniger gut wissenschaftlich evaluiert als bei Frauen. Außer Raloxifen und Östrogen/Gestagen kommen jedoch prinzipiell die gleichen Therapeutika in Betracht. Therapie der ersten Wahl sind die oral zu verabreichenden Bisphosphonate. Zugelassene Substanzen für die Indikation Osteoporose des Mannes sind Alendronat und Risedro- nat - bei schweren Osteoporosen auch dasTeriparatid. Die Androgentherapie sollte jüngeren Männeren mit eindeutigem Hypogonadismus vorbehalten bleiben und muss bei ausgeprägter Osteopenie evtl. durch gleichzeitige Behandlung mit anderen antiresorptiven oder osteoanabolen Medikamenten verstärkt werden.

Osteoporosis accounts for about 3 % of total European health-care spending. The low proportion of costs for the pharmacological prevention of osteoporotic fracture means that it is highly cost saving, especially in patient with severe osteoporosis or patients who cannot take certain osteoporosis medications due to issues of contraindications or tolerability. Following recent regulatory changes, strontium ranelate is now indicated in patients with severe osteoporosis for whom treatment with other osteoporosis treatments is not possible, and without contraindications including uncontrolled hypertension, established, current or past history of ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. We review here today's evidence for the safety and efficacy of strontium ranelate. The efficacy of strontium ranelate in patients complying with the new prescribing information (i.e. severe osteoporosis without contraindications) has been explored in a multivariate analysis of clinical trial data, which concluded that the antifracture efficacy of strontium ranelate is maintained in patients with severe osteoporosis without contraindications and also demonstrated how the new target population mitigates risk. Strontium ranelate is therefore an important alternative in today's management of osteoporosis, with a positive benefit-risk balance, provided that the revised indication and contraindications are followed and cardiovascular risk is monitored. The bone community should be reassured that there remain viable alternatives in patients in whom treatment with other agents is not possible and protection against the debilitating effects of fracture is still feasible in patients with severe osteoporosis.

Our trial was a 3-year, open-label, prospective, comparative, clinical study comparing the effects of oral alendronate (ALN), 10 mg daily, and alfacalcidol (AC), 1 microg daily, on bone mineral density (BMD), fracture events, height, back pain, safety and tolerability in 134 men with established primary osteoporosis. All men received 500 mg calcium daily. BMD was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (DXA). Spine radiographs were obtained at baseline and every 12 months thereafter, and were evaluated by a radiologist blinded to treatment assignment. At 3 years, AC-treated patients showed a significant mean increase of 3.5% in lumbar spine BMD, compared with a mean increase of 11.5% in men receiving ALN ( p0.0001 between groups). The corresponding increases in femoral neck BMD were 2.3% and 5.8% for the AC and ALN groups, respectively ( p=0.0015 between groups). Over 3 years, new vertebral fractures occurred in 24.2% of the AC-treated patients and in 10.3% of the ALN-treated patients ( p=0.040). ALN-treated patients also had a significantly lower height loss. There were no between-group differences regarding nonvertebral fractures or changes in back pain. Both therapies were well tolerated, with a compliance rate90%. We conclude that although AC has significant effects on BMD, ALN has greater effects on BMD and fracture efficacy.

Despite its well-known benefits, chronic corticosteroid therapy causes osteoporotic fractures in approximately 30-50% of patients treated. To prevent the occurrence of these fractures, treatment with oral bisphosphonates is recommended. However, current oral bisphosphonates, which are given either daily or weekly, are associated with stringent, inconvenient dosing guidelines. Less frequent dosing may provide greater acceptability. The objective of this study was to investigate the efficacy and safety of ibandronate, a highly potent nitrogen-containing bisphosphonate, when given by intravenous (i.v.) injection every 3 months in men and women with established corticosteroid-induced osteoporosis (CIO; lumbar spine [L2-L4] bone mineral density [BMD] T-scoreor =-2.5). A total of 115 participants were assigned to receive daily calcium supplements (500 mg) plus either ibandronate (2 mg) injections every 3 months or daily oral alfacalcidol (1 microg), for 3 years. Intermittent i.v. ibandronate injections produced significantly greater increases in mean BMD at the lumbar spine (13.3% versus 2.6%, respectively; p0.001), and femoral neck (5.2% versus 1.9%, respectively; p0.001) versus daily oral alfacalcidol, after 3 years, relative to baseline. This study was not statistically powered to show a difference between the groups with respect to fracture incidence. Nevertheless, after 36 months, the frequency of patients with new vertebral fractures was significantly lower in the patients receiving ibandronate relative to those taking alfacalcidol (8.6% versus 22.8%, respectively; p=0.043). This is the first time that significant vertebral fracture reduction has been demonstrated with an i.v. bisphosphonate in CIO. Patients treated with i.v. ibandronate injections also experienced less back pain (p0.001) and less height loss (p=0.001) than those receiving oral alfacalcidol. Both regimens were well tolerated. In conclusion, intermittent i.v. ibandronate injections are efficacious, well-tolerated, and convenient, and promise to offer physicians an important therapeutic advance in the management of osteoporosis.

Summary: This consensus article reviews the diagnosis and treatment of osteoporosis in geriatric populations. Specifically, it reviews the risk assessment and intervention thresholds, the impact of nutritional deficiencies, fall prevention strategies, pharmacological treatments and their safety considerations, the risks of sub-optimal treatment adherence and strategies for its improvement. Introduction: This consensus article reviews the therapeutic strategies and management options for the treatment of osteoporosis of the oldest old. This vulnerable segment (persons over 80years of age) stands to gain substantially from effective anti-osteoporosis treatment, but the under-prescription of these treatments is frequent. Methods: This report is the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores some of the reasons for this and presents the arguments to counter these beliefs. The risk assessment of older individuals is briefly reviewed along with the differences between some intervention guidelines. The current evidence on the impact of nutritional deficiencies (i.e. calcium, protein and vitamin D) is presented, as are strategies to prevent falls. One possible reason for the under-prescription of pharmacological treatments for osteoporosis in the oldest old is the perception that anti-fracture efficacy requires long-term treatment. However, a review of the data shows convincing anti-fracture efficacy already by 12months. Results: The safety profiles of these pharmacological agents are generally satisfactory in this patient segment provided a few precautions are followed. Conclusion: These patients should be considered for particular consultation/follow-up procedures in the effort to convince on the benefits of treatment and to allay fears of adverse drug reactions, since poor adherence is a major problem for the success of a strategy for osteoporosis and limits cost-effectiveness.

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 1 microgram alfacalcidol plus 5000 mg calcium (group A: n = 43) or with 1000 IU vitamin D plus 500 mg 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 (1alpha) compared with the native vitamin D(3) in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D(3) plus 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 1alpha (+2.0%, P0.0001) and no significant changes at the femoral neck. In the D(3) group, 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 1alpha and 21 in 17 patients of the D(3) group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P0.0001) 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.

Paradoxe Embolien sind in der Theorie gut bekannt, in der Praxis aber recht selten. Pathophysiologisch liegt typischerweise die Konstellation aus venoser Thrombose, erhohtem rechtsatrialen Druck und konsekutivem Rechts-Links-Shunt uber ein offenes Foramen ovale oder einen Vorhofseptumdefekt zugrunde. Wir berichten uber einen 65jahrigen 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 Vorfus blas, kalt und pulslos. Auserdem war der Patient tachypnoisch, tachykard und normoton. Im EKG Rechtsverspatung und SIQIII-Typ. Die Angiographie zeigte einen Verschlus der A. femoralis communis. Zunachst erfolgte die Embolektomie, anschliesend wurden in einem Lungenszintigramm multiple Lungenembolien beidseits festgestellt. Phlebographisch wurde eine Unterschenkelvenenthrombose rechts diagnostiziert. Unter dem Verdacht auf eine paradoxe Embolie wurde eine transosophageale Echokardiographie (TEE) durchgefuhrt. Diese ergab ein offenes Foramen ovale. Der vorliegende Fall stellt beispielhaft den Ablauf einer paradoxen Embolie bei patentem Foramen ovale dar. Eine Phlebothrombose fuhrt 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.

In an 81-year-old woman with primary hyperparathyroidism 2.5 ml of 95% ethanol were injected transthyroidally, under ultrasound control and local anesthesia, into a parathyroid adenoma, about 2.5 X 1.3 X 1.1 cm in size. Unilocular deposition of ethanol into the adenoma proved ineffective, but multilocular injection normalized serum calcium and parathormone concentrations. There were no complications. If the topography is favorable, this method can be an alternative to operation.

Obwohl in den letzten Jahren das Interesse an sekundaren Osteoporosen und an der Osteoporose bei Mannern [1] erheblich angestiegen ist, bleibt die postmenopausale Osteoporose der Frau die haufigste und soziookonomisch wichtigste Osteoporoseform [2, 3]. Sie fuhrt uber einen perimenopausal einsetzenden progredienten Knochensubstanzverlust [4] zu Wirbelbruchen mit akuten Ruckenschmerzen und schlieslich zu Rundrucken, Grosenverlust und einem chronischen Schmerzsyndrom. Erkennung von Risikopersonen mit dem Ziel der Pravention oder Diagnose von Osteopenien vor der ersten Fraktur mit dem Ziel der Fruhtherapie ist daher entscheidend zur Vermeidung einer manifesten Osteoporoseerkrankung [5, 6]. Ein bedeutsamer Risikofaktor fur die Osteoporose ist zwar der postmenopausale Ostrogenmangel, insgesamt aber ist die Pathogenese multifaktoriell. Die Verminderung der Risikofaktoren wird deshalb als lebenslange Aufgabe angesehen.

Vitamin D regulates the calcium-phosphate metabolism and thereby plays an important role for the integrity and functioning of bone, muscle and nerves. Studies have shown furthermore an influence on certain types of cancer, diabetes and cardiovascular diseases. Vitamin D is mainly produced by the skin. During exposure to sunlightthe precursor7-dehydrocholesterol is transformed to colecalciferol (vitamin D3). Smaller amounts are supplied by nutrition. In our latitude vitamin D synthesis takes only place during summertime. The vitamin stored in fat tissue in generally is not sufficient for the whole winter period and accordingly insufficiency is very frequent. In a cross-sectional study all over Germany (DeViD, 2007) only about 8% of the population was vitamin D sufficient in spring time.Two prospective studies (2008) proved a correlation between vitamin D supply and overall mortality. An amelioration of vitamin D supply can be achieved either by increasing sun exposure or daily oral intake of 800-2000 IU (=20-50 microg) colecalciferol.

The therapeutic strategy for the reduction of fracture risk in osteoporosis should not only aim to increase bone strength, but should also improve muscle function and reduce falls without increasing the risk of significant side effects. Since 2008 a combination therapy of the antiresorptive active bisphosphonatealendronate and the pleiotropic active D-hormone-prodrug alfacalcidol is licensed in Germanyfor treatment of postmenopausal osteoporosis (Tevabone).In the review the results of numerous preclinical and clinical studies are reported, showing the efficacy of the combination of alendronate plus alfacalcidol.In preclinical trials with ovariectomized rats the combination has shown a significantly better effect on increased bone turnover in comparison with bisphosphonate monotherapy. Presumably the "oversuppression" of bone remodeling and the resulting risk of reduced microfracture healing, which is known to occur after long-term therapy with bisphosphonates, will be reduced by the combination. Clinical studies have shown better efficacy of the combination in the increase of bone density and reduction of fracture rate (vertebral and non-vertebral fractures). Less falls were reported compared to alendronate plus genuine vitamin D. The reduction of increased parathormone levels by the alendronate plus alfacalcidol combination compared to alendronate alone was proven to increase the responder rate of the alendronate therapy. The potential risks of alendronate-induced hypocalcemia as well as alfacalcidol-induced hypercalcemia or hypercalcuria are reduced due to the contrasting mode of action of both compounds.Treatment with the alendronate plus alfacalcidol combination meets the demands of an optimized therapy for osteoporosis.With the especially developed, self-explanatory combination package better compliance and less dispensing mistakes can be expected.

Almost 50 % of osteoporosis (OP) patients discontinue bisphosphonate (BP) therapy within 1-2 years after the start of their treatment. Denosumab's longer dosing interval with its administration every 6 months (Q6M) as a subcutaneous (sc) injection might result in a better real-life treatment adherence and persistence than weekly or monthly oral BP treatment regimen. The objectives of this open, investigator-initiated, prospective, observational, single-center study were to evaluate adherence with denosumab 60 mg sc every 6 months (Q6M) (Prolia(®)) injections in osteoporotic patients in a routine clinical care setting and to describe whether positive feedback to OP patients based on measured bone mineral density (BMD) increases and good safety profile have an impact on patients' real-life adherence. Results indicate that the rarity of adverse events and reduced dosage frequency together with the consistency of rapid and highly significant increases in BMD already after 6 months of denosumab therapy used as a positive reinforcement during doctor-patient interactions had a significant, positive impact on osteoporotic patient's adherence to continue with the 6-monthly sc denosumab injections.

This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy in glucocorticoid-induced osteoporosis (GIO). From this observational study, alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The effectiveness of each bisphosphonate is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials (RCTs). This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy with fracture incidence during a short period after starting a therapy. The study population was a subgroup of a larger cohort study comprising two cohorts of women aged ≥65 years, prescribed with alendronate or risedronate. Within the two study cohorts, 11,007 women were identified as having received glucocorticoids. Within each cohort, the baseline incidence of clinical fractures at nonvertebral and vertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baseline data, we then compared the fracture incidence during the subsequent 12 months on therapy. The baseline incidence of clinical nonvertebral and vertebral fractures was similar in the alendronate cohort (5.22 and 5.79/100 person-years, respectively) and in the risedronate cohort (5.51 and 5.68/100 person-years, respectively). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12 months in both cohorts of alendronate (33 % lower at nonvertebral sites and 59 % at vertebral sites) and risedronate (28 % lower at nonvertebral sites and 54 % at vertebral sites). From this observational study not designed to compare drugs, both alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The reductions observed in fracture incidence, within each cohort, suggest that the effectiveness of each bisphosphonate in clinical practice is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials.

Osteoporosis is listed by the WHO among the ten most frequent and socio-economically important, chronic diseases of mankind. The term osteoporosis however comprises a number of different pathophysiological conditions and clinical situations of weakened bones with increased risk of fragility fractures. A modern anti-osteoporotic drug should provide qualified study results proving therapeutic efficacy over this broad range of daily clinical appearances of osteoporosis. The decision for treatment in the individual patients depends no longer only on bone mineral density. Today, the major criterion for decision making is the prospective 10-year risk for fractures. Since this risk is calculated on the basis of age, sex, bone mineral density, prevalent fractures, and a number of other contributing risk factors (Kanis et al., Osteoporos Int 12:989-995, 2001; Kanis et al., Osteoporos Int 19:385-397, 2008), it seems to be of interest to have a look whether the fracture-reducing potency of a drug is influenced by these risk factors. The purpose of this review is to analyze whether the fracture-reducing efficacy of strontium ranelate in patients with osteoporosis can be achieved independently of sex, etiology of osteoporosis, and the major diagnostically relevant risk factors.

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.

Generalized idiopathic osteoporosis and transient osteoporosis of the hip are both rare complications of pregnancy. More frequently, long-term heparin administration to treat deep thrombosis in the legs or pelvis may lead to substantial decreases in bone mass and consequently increased risk of osteoporosis. Therapeutic studies with the aim to counteract the osteoporosis inducing effect of heparins, have not been published to date. In the special situation of pregnancy, most medications used for osteoporosis are contraindicated. In our open randomised study, 9 women on heparin-treatment received daily 6.46 g of the bone preparation OHC (ossein-hydroxyapatite-compound) over a period of 6 months and were compared to 11 women without bone protective treatment. In the OHC-group, good compliance was observed with no side effects and reduced back pain. Bone mass did not change significantly, whilst it dropped significantly statistically in the controls.

There are no general accepted strategies for combined drug treatments in osteoporosis, while in other important chronic diseases combinations of different medications are used as a rule to improve therapeutic results and reduce the risk of adverse events. It is suggested that the success of combined treatments is related to the different modes of action of the respective single therapies. On the other hand it was shown that a strong antiresorptive bisphosphonate is able to blunt at least in part the effects of anabolic parathyroid hormone peptides Calcitriol, the active vitamin D-hormone and its prodrug alfacalcidol lead to pleiotropic effects on bone remodelling (antiresorptive, anabolic and enhancing mineralization) and in addition to effects on other important target tissues (e.g. gut, parathyroid glands, muscle). With active D-analogs significant improvements in the therapeutic outcome of osteoporosis can be achieved by the resulting improvements of bone quality, calcium absorption and risk reduction of falling. The same beneficial effects cannot be achieved with plain vitamin D due to feedback controlled, limited renal activation or insufficient conversion in the elderly with impairment of renal function. Accordingly alfacalcidol, approved as a treatment for different forms of osteoporosis, is besides adoption as a mono-therapy an interesting candidate for combined therapies. There are interesting preclinical trials and clinical pilote studies in the literature proving that a parallel therapy with selectively anti-osteoclastic bisphophonates and pleiotropically acting D-analogs is able to optimize therapeutic results in osteoporosis. In the AAC-Trial (Alfacalcidol-Alendronate-Combined) we studied 90 patients with established osteoporosis (57 women, 33 men) over two years after alternate allocation to three treatment arms (alfacalcidol plus calcium, alendronate plus plain vitamin D and Ca, and alendronate plus alfacalcidol and Ca). During the 2-year-study we observed the significantly highest lumbar spine and hip BMD increases in the combined treatment group (p < 0.001). The number of patients with new vertebral and non-vertebral fractures after 2 years was 9 with alfacalcidol alone, 10 with alfacalcidol and plain vitamin D and 2 in the group receiving alendronate plus alfacalidol (p < 0.02). Furthermore there was a lower rate of falls and an earlier reduction in back pain in the patients treated with the active combination. This trial confirms the demonstrated highly significant advantages of this combined treatment regimen used in the pilote studies. Especially in patients with severe osteoporosis this interesting combination of two substances with complete different mechanisms of action should be taken into consideration.