Katharina Kerschan-Schindl

Osteoporosis: An Age-Related and Gender-Specific Disease – A Mini-Review

Osteoporosis, a classical age-related disease and known to be more common in women than in men, has been reported increasingly often in men during the past few years. Although men at all ages after puberty have larger bones than women, resulting in greater bending strength, mortality after a hip fracture, one of the major complications of osteoporosis, is more common in men than in women. Sex hormone deficiency is associated with unrestrained osteoclast activity and bone loss. Even though estrogen deficiency is more pronounced in women, it appears to be a major factor in the pathogenesis of osteoporosis in both genders. In contrast to osteoporosis in postmenopausal women, the treatment of osteoporosis in men has been scarcely reported. Nevertheless, some drugs commonly used for the treatment of osteoporosis in women also appear to be effective in men. The aim of this study is to review primary osteoporosis in the elderly with particular emphasis on gender-related aspects.

Measuring health in patients with fibromyalgia: Content comparison of questionnaires based on the International Classification of Functioning, Disability and Health

OBJECTIVE To analyze the content of outcome measures commonly used to assess health in patients with fibromyalgia (FM) by linking the items of the instruments with the International Classification of Functioning, Disability and Health (ICF) in order to evaluate the adequacy of currently used measures. METHODS Questionnaires used in FM were identified in a structured literature search. All concepts included in the items of the questionnaires were linked to ICF categories, according to previously published linking rules, by 2 independent health professionals. The percentages of linked ICF categories addressing the different ICF components were calculated. RESULTS Generic and symptom-specific instruments were included. From the 296 items contained in all 16 instruments, 447 concepts were extracted and then linked to 52 ICF categories of the component body functions, 1 category of the component body structure, 40 categories of the component activities and participation, and 9 categories of the component environmental factors. More than half of the concepts identified were linked to body function, fewer were linked to activities and participation, and only concepts of 4 instruments were linked to the ICF component environmental factors. CONCLUSION Many concepts were linked to the categories in the ICF component body functions. While linking to the broad category, purportedly similar instruments often covered widely varying areas of function at more fine-grained levels of detail. Some categories, such as environmental factors, were barely covered by any of the instruments and might constitute an important aspect of health deserving better coverage and future development.

Pathophysiology of osteoporosis

ZusammenfassungDie Osteoporose ist eine klassische altersassoziierte Erkrankung, welche Frauen häufiger als Männer betrifft. Die Hypothese, daß die Osteoporose infolge einer Östrogendefizienz auftritt, wurde bereits 1941 von Albright et al. [1] aufgestellt. Die molekularbiologischen Wirkungsmechnismen der Östrogendefizienz postmenopausaler Frauen sowie älterer Männer werden in einer Vielzahl laufender Studien untersucht. Die Östrogendefizienz hat sowohl direkte als auch indirekte Einflüsse auf den Knochenmetabolismus, welche allesamt zu einer intensivierten Osteoklastogenese führen. Diese Übersichtsarbeit beleuchtet sowohl die endokrinologischen als auch die osteoimmunologischen Mechanismen, die zur Involutionsosteoporose führen.SummaryOsteoporosis is a classical age-related disease that affects women more often than men. The hypothesis that osteoporosis is a consequence of estrogen deficiency, has been proposed as early as 1941 by Albright and colleagues [1]. The exact mechanisms of this steroid hormone deficiency in postmenopausal women as well as in the elderly men are continuously being unraveled. Collectively, estrogen deficiency has direct as well as indirect impacts on bone metabolism all of which promote osteoclastogenesis. This review aims at shedding light on the endocrine and osteoimmunological mechanisms that lead to involutional osteoporosis.

Pathogenesis of bone loss in heart transplant candidates and recipients.

BACKGROUND Heart transplantation (HTX) is associated with decreased bone mineral density and changes in bone metabolism. We conducted this study to evaluate the pathophysiology of bone metabolism in HTX candidates and recipients. METHODS Thirty-six HTX recipients were compared with 36 HTX candidates concerning biochemical parameters of bone metabolism and bone mineral density. RESULTS Osteocalcin, bone-specific alkaline phosphatase, cross-linked-N-telopeptide of type I collagen, estradiol, serum creatinine, and blood urea nitrogen concentrations were significantly higher, whereas the calcium-creatinine ratio, thyrotropin, thyroxine, and bone mineral density were significantly lower in HTX recipients than in HTX candidates. Compared with a control group, HTX candidates had decreased renal function and increased bone resorption, whereas HTX recipients additionally had increased alkaline phosphatase and osteocalcin levels. In HTX recipients, we found positive correlations between creatinine clearance and bone mineral density; daily and cumulative cortisone doses were not associated with bone mineral density. CONCLUSIONS In HTX candidates, disturbances in bone metabolism with increased bone resorption may be caused partly by existing low-grade renal insufficiency, regular intake of loop diuretics, and restriction of mobility. In HTX recipients, immunosuppressive therapy-glucocorticoids and cyclosporine-seem to be responsible for changes in bone metabolism.

A 246-km continuous running race causes significant changes in bone metabolism

BACKGROUND Regular physical exercise exerts a favorable effect on the skeleton. However, excessive physical exercise may have detrimental effects. A low bone mineral density (BMD) has been registered in highly trained runners. The aim of the present study was to evaluate potential effects of the Spartathlon, an annual ultramarathon race of 246 km, on bone metabolism. METHODS Venous blood samples were taken before and within 15 min after the end of the race as well as three days after the start of the race. The following variables of bone metabolism were studied: osteocalcin (Oc), cross-linked-C-telopeptide of type I collagen (CTX), osteoprotegerin (OPG), and its ligand, receptor activator of nuclear factor kappaB ligand (RANKL). RESULTS Blood samples were taken from 18 runners (16 men and 2 women) at the three time points. The median time taken by the runners to complete the race was 32 h and 52 min. Serum levels of CTX were significantly increased immediately after the race as well as three days after the start of the race compared with the time prior to the race. Oc was transiently suppressed after the race. Serum levels of RANKL and OPG were increased three days after the start of the race compared to the time before the start of the race. CONCLUSIONS This study showed that an ultra-distance run of nearly 250 km induced changes in RANK/RANKL/OPG interaction, which suggests a transient uncoupling of bone metabolism, increased bone resorption, and suppressed bone formation.

Long-term outcome after treatment of temporomandibular joint osteoarthritis with exercise and manual therapy.

ABSTRACT In a previous study, exercise and manual therapy demonstrated a 90% success rate in patients with osteoarthrosis of the temporomandibular joints in the short-term. The aim of this follow-up study was to assess the long-term effect of these treatment modalities. Seventeen patients were evaluated. All patients suffered from osteoarthrosis of the temporomandibular joints with pain in the temporomandibular joint at baseline and were treated successfully in a prior short-term study. The parameters were pain at rest and at chewing, impairment in daily life, and mouth opening. At follow-up, 11 patients (65%) experienced no pain and 13 patients (76%) had no pain at rest (Fishers Exact Test: p<0.02). Thirteen patients (76%) had a normal incisal edge clearance, and ten patients (59%) felt no impairment due to the disease (Fishers Exact Test: p=0.01). Thirteen patients (76%), who had been treated once successfully, have not needed treatment within the three years after cessation of their therapy. Exercise therapy is an effective tool to treat osteoarthrosis of the temporomandibular joints.

High Cathepsin K Levels in Men with Differentiated Thyroid Cancer on Suppressive L-Thyroxine Therapy

BACKGROUND Thyroid hormone administration is associated with low bone density in some studies. The aim of the present study was to evaluate the influence L-thyroxine, in doses used to treat patients with a history of thyroid carcinoma, on serum cathepsin K and other markers of bone metabolism. Cathepsin K is thought to have a role in osteoclast mediated bone resorption. METHODS A group of male patients with differentiated thyroid cancer (DTC) on suppressive L-thyroxine therapy (DTC-group; n = 51; mean age 57 years; TSH < 0.1 mU/L) was selected as a model for hyperthyroidism. The results were compared to a group of healthy euthyroid men (control-group; n = 50; mean age 58 years; TSH 1.5 +/- 0.9 mU/L). RESULTS In the DTC-group the median value of cathepsin K was 6.9 pmol/L, in the control group 4.8 pmol/L (p = 0.0052; highly significant [h.s.]). There was a significant negative correlation of cathepsin K with age (r = -0.279, p = 0.028). The analysis of various bone associated parameters revealed an increase of serum crosslaps in the DTC-group versus euthyroid controls (p = 0.03). A significant correlation could be found for cathepsin K and osteoprotegerin (p = 0.002). CONCLUSION Cathepsin K is increased by a suppressive L-thyroxine therapy and decreases with increasing age. The increased cathepsin K levels seen in DTC-patients on suppressive L-thyroxine therapy are likely to contribute to accelerated bone degradation in these patients.

Changes in Serum Levels of Myokines and Wnt-Antagonists after an Ultramarathon Race.

Background Regular physical activities have a positive effect on the muscular skeletal system but overstrenuous exercise may be different. Transiently suppressed bone formation and increased bone resorption after participation in a 246-km ultradistance race has been demonstrated. Purpose The aim of this study was to analyze effects of the Spartathlon race on novel musculoskeletal markers. Methods Venous blood samples were obtained before and immediately after the race from 19 participants of the Spartathlon. From 9 runners who were available 3 days after the start blood was drawn for a third time. Serum levels of myostatin, an inhibitor of myogenic differentiation, and its opponent follistatin as well as sclerostin and dickkopf-1, both of them inhibitors of the wnt signaling pathway, and markers of bone turnover were determined. Results Serum levels of myostatin were significantly higher after the race. Serum follistatin only showed a transient increase. Sclerostin levels did not significantly differ before and after the race, whereas dickkopf-1 levels were significantly decreased. At follow-up a decrement of sclerostin and dickkopf-1 levels was seen. Serum cathepsin K levels did not change. Conclusion The increase of serum levels of myostatin appears to reflect muscle catabolic processes induced by overstrenuous exercise. After the short-term uncoupling of bone turnover participation in an ultradistance race seems to initiate a long-term positive effect on bone indicated by the low-level inhibition of the Wnt/β-catenin signaling pathway.

Bone Metabolism in Patients with Primary Hyperparathyroidism Before and After Surgery

Primary hyperparathyroidism (PHPT) is accompanied with a reduced bone mineral density (BMD) and an increased risk of fracture. Surgery is the only option for cure. It is hypothesized that in patients with PHPT bone metabolism normalizes after parathyroidectomy (PTX) and that BMD gradually increases. Fifty-two patients with PHPT who underwent surgery were prospectively followed for 1 year. Biochemical analyses were performed at baseline and 1, 4, 7 days; 6 weeks; and 3, 6, and 12 months, and BMD before and one year after surgery. Parathyroid hormone (PTH), calcium, and the bone resorption marker dropped immediately, but transiently after PTX, bone formation decreased more slowly. Osteoprotegerin (OPG) as well as cathepsin K did not show significant changes. BMD of the lumbar spine, but not of the femoral neck, increased significantly within one year after surgery. Moderate correlations existed between the changes of total calcium, ionized calcium, as well as bone-specific alkaline phosphatase and changes of the lumbar BMD. Patients who needed postoperative supplementation with calcium and vitamin D had significantly higher PTH levels. Some gender-specific differences in patients with PHPT were observed. In patients with PHPT, males appear to be more severely affected than females. Within the first year after PTX, bone metabolism normalized, and BMD of the lumbar spine increased. Patients who needed a supplementation with calcium and vitamin D after PTX preoperatively had higher serum levels of PTH.

Osteoporosis: Gender-specific aspects

SummaryTraditionally, osteoporosis has been regarded as a disease of postmenopausal women; nevertheless, although osteoporosis is more common in women than in men, osteoporosis in men is a frequent and a severe condition. Osteoporosis generally can be characterized as either primary or secondary; in men secondary osteoporosis is more frequent than in women. The role of estrogen deficiency in the pathogenesis of postmenopausal osteoporosis is clearly established; remarkably, evidence accumulated over the past years strongly suggests that estrogen also plays the dominant role in regulating the male skeleton. Several independent studies observed decreased serum estradiol levels in men with idiopathic osteoporosis. In contrast to postmenopausal osteoporosis, there are only few studies on the treatment of osteoporosis in men; two different compounds (alendronate and teriparatide) appear to be equally effective in men and women.ZusammenfassungDie Osteoporose wird weitgehend als eine Erkrankung der postmenopausalen Frau angesehen. Obwohl nicht ganz so häufig wie bei den Frauen, kommt es aber auch bei Männern zu osteoporotischen Frakturen. Entsprechend der Ätiologie wird eine primäre von einer sekundären Osteoporose unterschieden. Frauen leiden häufiger an einer primären Osteoporose, Männer häufiger an einer sekundären Osteoporose. Die Östrogendefizienz ist der wesentlichste Faktor bei der Entstehung der postmenopausalen Osteoporose. Mehrere Untersuchungen zeigten auch bei Männern mit idiopathischer Osteoporose erniedrigte Serumöstradiolspiegel auf. Es ist somit wahrscheinlich, dass das weibliche Sexualhormon auch beim männlichen Knochenstoffwechsel eine entscheidende Rolle spielt. Die Therapie der postmenopausalen Osteoporose ist wesentlich häufiger untersucht worden als jene der männlichen Osteoporose. Die Substanzen Alendronat und Teriparatid scheinen aber bei Frauen und Männern gleich effektiv zu sein.