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In October 2023, the organization of the German-speaking scientific osteological societies (DVO) published the revised guideline on the "Prophylaxis, diagnosis and treatment of osteoporosis in postmenopausal women and in men aged over 50." This review article reflects the new features of the guideline and their relevance in the care of patients with inflammatory rheumatic diseases.A key innovation is the change from the 10-year fracture risk to the 3‑year fracture risk. Basic diagnostics are currently performed without a defined fracture threshold. Treatment thresholds for specific osteological therapy constitute another key innovation, defined as 3% to < 5%, 5% to < 10%, and from 10% for vertebral body and femoral neck fractures. If the 3‑year fracture risk is > 10%, osteoanabolic therapy should primarily be carried out and antiresorptive therapy is initiated following osteoanabolic therapy. In addition, patients with osteoporosis and prolonged glucocorticoid therapy should primarily be treated osteoanabolically with teriparatide. In summary, the changes to the DVO guideline reflect the latest scientific study findings in osteology and lead to detailed differential therapy for osteoporosis., (© 2024. The Author(s).)

Background: Osteopenia (OP) or osteoporosis (OST) was diagnosed by bone densitometry (DXA) in postmenopausal women free of known skeletal disorders and without acute fracture. DVO guidelines were applied to define therapeutic indication., Methods: The study included 94 women aged 59-81 years. Fracture or operation ≤12 months, malignant tumor, ovariectomy, and drugs such as cortisone, strontium, fluorides, bisphosphonates, SERMs, estrogens, and steroids were exclusion criteria. The lowest T-score at the spine, femoral neck, or total hip was decisive. The indication for therapy was determined by evaluating age, BMD, and other risk factors., Results: Using the WHO criteria 22.3% (n=21) had normal BMD, 52.1% (n=49) had OP, and 25.6% (n=24) had OST. According to "Dachverband Osteologie" (DVO) guidelines, 28 women (29.8%) of the whole group needed therapy. Of the 28 women receiving therapy, 9 had OP and 19 had OST. Therapy was indicated in 18.4% for OP and 79.2% for OST., Conclusion: A preventive measurement of BMD with DXA provides a benefit for postmenopausal women. Combinatory assessment and consideration of other risk factors allows identification of women who might benefit from early treatment.

The primary goal of treatment for postmenopausal osteoporosis is the reduction in fracture risk. Bisphosphonates have long been established as first-line therapy for osteoporosis and several of these drugs significantly reduce osteoporotic fracture risk. Alendronate, risedronate, ibandronate and zoledronic acid all provide fracture protection for patients with postmenopausal osteoporosis. All four agents have demonstrated efficacy in preventing vertebral fractures, but only zoledronic acid and risedronate significantly reduce non-vertebral fracture risk in pivotal trials. Moreover, reduction in hip fracture risk has been established for alendronate, risedronate and zoledronic acid. Ibandronate and zoledronic acid have the most persistent antifracture effect. Bisphosphonates have been associated with a number of side effects, with a well-documented association between gastrointestinal adverse events and oral administration, and between acute phase reactions and intravenous administration.

The recombinant amino-terminal fragment of human parathyroid hormone (Teriparatide) is a bone anabolic agent which reduces fracture risk by increasing bone mass and improving bone microarchitecture. Teriparatide reduces vertebral fracture risk by 65 % and non-vertebral by 50 %. Its efficacy is higher as bisphosphonates to prevent corcicosteroid-induced osteoporosis. Teriparatide may also have a direct effect on bone pain. Teriparatide may be initiating immediately after an anticatabolic agent. However, it is not recommended to associate both treatments. At the end of teripatide treatment, an anticatabolic agent may be given. According to cost-effectiveness studies, Teriparatide should be considered as first line treatment for postmenopausal women and for men with severe osteoporosis.

The three modern Selective Estrogen Receptor Modulators (SERMs) Raloxifene, Lasoxifene and Bazedoxifene registered in Europe reduce in postmenopausal women with a high risk for osteoporosis the incidence of vertebral fractures by 30 - 50 %, depending on the subgroup they belong to. Solid prospective fracture data for risk reduction in non-vertebral fractures, including the hip, are missing for Raloxifene and Bazedoxifene. However, a post hoc analysis suggests that the risk for non-vertebral fractures is significantly reduced by Raloxfene in women with severe osteoporosis. The simultaneous decrease of the incidence of ER-positive invasive breast cancer in Raloxifene users is highly relevant for clinicians. Unfortunately, Raloxifene and Bazedoxifene are, in the EU and in Switzerland, only labelled for the use in the prevention and treatment of postmenopausal osteoporosis. SERMs may induce or augment vasomotor symptoms. Therefore, SERMs are not a first line therapy in early postmenopause. Looking at other hormonal options, Hormone Replacement Therapy (HRT) remains the first line therapy for fracture reduction in the peri- and early postmenopause. SERMs are an appropriate choice for the continuation of fracture prevention after an initial HRT, particularly for the prevention of vertebral fractures. SERMs are safe if (as in oral HRT) the slightly increased risk for venous thrombo-embolism is respected. In conclusion, SERMs have today their well established place in the prevention and treatment of postmenopausal osteoporosis, particularly in women with a simultaneously increased breast cancer risk.

Denosumab is the first human monoclonal antibody for the treatment of osteoporosis. By inhibiting RANK Ligand, Denosumab prevents the development, activation and survival of osteoclasts. The FREEDOM study reported a 68 % reduction of vertebral fractures, 20 % of non-vertebral fractures and 40 % of hip fractures after 3 years in post-menopausal women with osteoporosis receiving denosumab 60 mg sc every six months vs. placebo. Five years extension of the denosumab group showed a further decrease in the rate of both vertebral and non-vertebral fractures, whereas BMD at spine and hip increased continuously. There was no increase in the rate of adverse events year after year, including of infections, cancer, atypical fractures, delayed fracture healing or ONJ. Clinical hypocalcemia was rare in the context of calcium and vitamin D supplementation. Pre-planned and post-hoc subgroup analyses have further shown the anti-fracture efficacy of denosumab in high-risk subgroups, such as older women and those with low T-scores and/or prevalent vertebral fractures. Denosumab withdrawal is accompanied by a transient rebound of bone turnover markers and a proportional BMD loss. Smaller randomized controlled studies have shown that denosumab further improves BMD after one year compared to alendronate.

Background and Objective: Whole body vibration (WBV) training is a new approach which is currently discussed in the context of reducing the risk of osteoporotic fractures. The study was undertaken to determine the effect of one-year WBV exercise on bone mineral density (BMD) and the number of falls., Methods: 151 postmenopausal women (68.5 +/- 3.1 years) were randomly assigned to three groups: (1) conventional (multifunctional) training (TG); (2) multifunctional training including WBV (VTG); (3) wellness-control group (CG). The training groups performed multifunctional training twice weekly (60 min; dancing aerobics, balance training, functional strength training). In the last 15 min of each session, leg strength exercises on vibration platforms were performed. The plates were switched on only in the VTG. The CG performed a low intensity gymnastic and relaxation programme (4 x 10 sessions of 60 min). BMD was measured at the hip and lumbar spine at baseline and after 12 months with the DXA method. Falls were recorded daily with the calendar method in a fall log., Results: An increase in BMD at the lumbar spine was measured after one year in both training groups (VTG: + 1.17 +/- 2.4 % vs. TG: + 1.73 +/- 2.4 %). The difference between the TG and the CG was significant (p < .05). Regarding the hip region a loss was noted in the CG (- 0.9 +/- 2.5), whereas the BMD stayed stable in the training groups (TG: - 0.3 %; VTG: + 0.1 %). The fall rate was significantly lower in VTG compared to CG (0.43 falls/person/year (VTG) vs. 1.14 (CG)., Conclusion: The multifunctional training resulted in a gain of BMD at the lumbar spine. Vibration training did not enhance the effect on bone but significantly reduced falls.

Hormone therapy with estrogens (combined with progestin for women who have not been hysterectomized) is the most efficacious treatment for climacteric symptoms. A few years ago hormone therapy was considered to be an ideal prevention for cardio-vascular disease, osteoporosis, dementia and other diseases. Large prospective randomized trials have changed this paradigm. Hormone therapy should only be used with a clear indication (moderate to severe climacteric symptoms and - with limitations - prevention of osteoporosis). The lowest effective dose should be used for the shortest possible time.

In the last 30 years bisphosphonates have been used in the treatment of different bone diseases. Bisphosphonates in their oral pharmaceutical form are an established and approved medication in osteoporosis treatment for years. Latest research developed more potent bisphosphonates in different application forms: oral and parenteral. Therefore, their prospects for medical treatment could be enlarged to the fields of oncology, hematology, and osteology. Bisphosphonates are innovative in case of adjuvant therapy as well as in adequate pain therapy. In the medical treatment of osteoporosis and metabolic osteopathies bisphosphonates could be rightly denoted as groundbreaking.

Hormonal replacement therapy (HRT) with estrogens and gestagens has been used for more than 40 years in the treatment of menopausal complaints and can be considered an effective treatment for vaso-vegetative symptoms and urogenital atrophy. During the past few years many women and doctors have revised their opinions of HRT. The reasons for this change of view are mainly three large international studies: the Heart and Estrogen/Progestin Study, the Women's Health Initiative Study and the One Million Women Study. In this review we summarize the data from the most important studies and point out the actual status of the controversial discussion on the benefits and risks of HRT.

The menopausal transition is a natural phase of every womańs life. Several symptoms emerging during the climacteric may be treated with estrogens. Hot flushes and symptoms of genital ageing may be relieved by estrogen therapy. Progestin therapy is indicated in all women with an intact uterus to avoid endometrial pathology. Given the present risk-benefit scenario, estrogen therapy is no longer a first-line choice to prevent osteoporosis. Counselling requires integration of recent knowledge provided by the first results of the Womeńs Health Initiative and other significant randomized, placebo-controlled, prospective clinical studies with clinically relevant outcomes, not the least unless good-quality data regarding other estrogens and progestins, apart from conjugated equine estrogens/medroxyprogesterone acetate are lacking. Women should be enabled to decide upon estrogen therapy after provision of extensive information by their physicians.

While the use of hormone replacement therapy (HRT) for prophylactic indications such as cardiovascular disease, osteoporosis, and Alzheimer's disease was increasingly propagated during the 1990s, recent studies have reported no risk reduction for women after myocardial infarction (HERS) or women from a mixed population with an average age of 63 years (Women's Health Initiative [WHI] Study). The results of the latter study even suggest an increased risk for cardiovascular events and breast cancer with previous or ongoing combined oral estrogen plus progestin. A final risk-benefit assessment for estrogen monotherapy will only be possible after the ongoing part of the WHI Study has been evaluated, expected in 2005. As effects, side effects, and contraindications for HRT in postmenopausal women are better known, the need for individualized risk assessment and the definition of therapeutic goals increases. Since the WHI Study did not address the risk-benefit ratio for women with perimenopausal complaints or osteoporosis or with lower dose hormone preparations commonly used in Germany, there is an urgent need to answer these open questions with large confirmative studies.

The soy-isoflavones genistein and daidzein and the flaxseed-lignans secoisolariciresinol and matairesinol belong to the group of phytoestrogens. Epidemiological data suggest that phytoestrogens have a preventive effect against various estrogen-related diseases/symptoms such as breast cancer, menopausal symptoms, cardiovascular diseases, and osteoporosis. To prove these assumptions, available controlled clinical trials have been critically reviewed. Especially soy-isoflavones have been extensively studied. There is no scientific evidence for an effect of phytoestrogens on menopausal symptoms and risk factors of breast cancer. However, isoflavones-containing soy protein can lower total cholesterol, LDL cholesterol, and triglyceride serum levels. The strongest evidence exists for a preventive effect of soy isoflavones on postmenopausal bone loss of the lumbar spine. Distinct effects on estrogen-related diseases can be explained at least in part by the different affinity of isoflavones to estrogen receptors alpha and beta and the distinct tissue distribution of these receptors.

Within the last fifteen to twenty years extensive discussions were held about advantages and disadvantages of postmenopausal hormone replacement therapy. Basing on recent data from prospectively randomized studies the long-term application of a combined estrogen-gestagen therapy for general prophylaxis cannot be recommended. Ongoing studies are expected to provide sufficient data to determine regimens for the prevention of osteoporosis, development of cancer, and cardiovascular diseases.

The present article discusses the difficulties in using data from a meta-analysis of the effects of hormone replacement therapy on non-vertebral fractures. Comparison between the fracture data extracted from the primary studies and the data included in the meta-analysis showed discrepancies for the primary endpoint in three out of 14 studies. Since the complex decision processes behind meta-analyses are often not transparent to the reader it is recommended to provide further details on decision processes for data collection, selection and inclusion criteria for unpublished data. This information could be made available on the website of the publishing journal.

Summary: Vitamins and trace elements are largely provided by a balanced nutrition. In industrialized countries, though, frequent deficiencies occur e.g. in folic acid and vitamin D as well as iodide, iron and calcium. A short review of recommended daily intake is presented.

Osteoporosis is defined by an abnormal high loss of bone mineral. This loss leads to fractures of vertebral bodies as of the femoral neck with dramatic consequences. Therefore it is necessary to regard osteoporosis as a disease rather than normal aging process. Diagnosis of osteoporosis is based on clinical examination and measurement of bone-mineral density. Beyond life-style changing interventions pharmacological treatment in a stepwise approach is recommended. Supplementation with Vitamin D and calcium is the mainstay of therapy with individual addition of bisphosphonates or other substances. The specific ways for decision making are exemplified with special regard to their individual advantages and disadvantages.

ERT (estrogen replacement therapy) or HRT (hormone replacement therapy) can be employed for the prevention/treatment of various hormone-related conditions. The main indications are the treatment of psychovegetative deficits and--in part--primary prevention of osteoporosis. For other (hormone-related) diseases such as certain malignant tumors, the risk may increase under replacement treatment, so that a risk/benefit evaluation should always precede it prescription. Side effects of ERT/HRT include a greater risk of thrombosis and, possibly, a increase in cardiovascular events, so that this form of treatment cannot be recommended at least for the secondary prevention of cardiovascular disease. In general, treatment must be matched to the requirements and wishes of the patient. With increasing age and remitting symptoms, the dose can be reduced. Alternative substances such as phytoestrogens or selective estrogen receptor modulators (SERMs) extend the spectrum of therapeutic options.

Hormone replacement therapy (HRT) with estrogens (in non-hysterectomized women with estrogens and progestins) during the peri- and postmenopausal period has been widely applied for many years. On the basis of new data, HRT is currently being critically reviewed. HRT administered for up to 5 years to treat climacteric hot flashes, mood changes and sleep disturbances continues to be advocated and is largely safe. When HRT is used for longer periods, as required for the prevention of osteoporosis, a possible increase in the relative risk for breast cancer must be considered. Correctly applied in combination with an adequate dose of progestins, HRT can avoid an increase in the endometrial cancer risk. HRT is no longer recommended for secondary prevention of cardiovascular disease, and its use in primary prevention has not been convincingly demonstrated. The hoped-for efficacy of HRT in the prevention of Alzheimer's disease has not been confirmed by the data. Selective estrogen receptor modulators (e.g. Raloxifene) and biphosphonates are efficacious drugs for the prevention and treatment of osteoporosis. For women at risk of developing cardiovascular disease, changes in lifestyle, lipid-lowering drugs (statins), blood pressure control, use of acetylsalicylic acid, among others, have well-documented efficacy in primary and secondary prevention.

Oral contraceptives (OC) with 20 or 30 mcg Ethinyl-Estradiol (EE) inhibit bone remodeling in all age groups investigated until today as far as the biochemical parameters are considered. In perimenopausal women, OC with 20 or 30 mcg EE reduce the decrease in bone density and may, depending on the starting point, induce an increase in bone density. OC with 20 mcg EE might impede the formation of a physiological peak bone mass in very young women (probably women less than 20 years of age) by a reduction of bone metabolism. This possibility provoked a certain insecurity. However, it should not lead to the consequence that a safe contraceptive method is refused to young women. Unfortunately, there is still a lack of reliable studies allowing a final statement on the effect of low-dose OC on bone density in teenagers. Such studies are urgently needed so that we are able to guarantee in very young women that a reasonable contraception has not to be payed by a long-term risk for the skeletal health. The administration of a progestagen-only pill might be an alternative method for contraception in adolescence. A preparation containing 30 mcg of Levonorgestrel, nearly out of use today, could be of particular interest. A British study (20) has shown that during regular peroral administration of 30 mcg Leveonorgestrel per day, mean serum estradiol concentration decreased only slightly, from 653 to 500 pmol/l. This Estradiol concentration should still allow a normal bone metabolism and therefore a normal formation of the peak bone mass. However, the data actually available do not point convincingly to the conclusion that OC with 20 mcg EE or less might result in an insufficient estrogen concentration for normal bone metabolism. To reach peak bone mass, other factors than estrogens only are needed, such as Calcium, Vitamin D and physical activity.

For many years, hormone replacement therapy (HRT) has been regarded as one of the most reliable means of prophylaxis and treatment for postmenopausal osteoporosis. As HRT ameliorates menopausal symptoms, it is widely prescribed among early postmenopausal women. A variety of different modes of replacement that suit each individual requirement are available in terms of schedule (cyclic or combined application of gestagens) and route of application (oral or transdermal). HRT effectively prevents spinal bone loss and delays bone loss at the hip up to a very old age. With continued use after menopause, HRT might theoretically halve the incidence of vertebral and hip fractures. However, long-term use or use of HRT in old age is rarely practiced, and the actual benefit of a transient use for future fracture prevention remains unclear. Raloxifene is the first member of the novel class of selective estrogen receptor modulators (SERMs) that has been approved for the prophylaxis and treatment of postmenopausal osteoporosis. It combines the positive effects of estrogen on the skeleton with estrogen-antagonistic effects on sex tissues. Thus, raloxifene maintains bone mass and decreases the incidence of vertebral fractures in osteoporotic women, but avoids many of the side effects that are responsible for the poor long-term compliance to HRT such as resumption or continuation of regular menses, breast tenderness, or breast cancer. It even markedly reduces the risk of breast cancer. Both estrogen and raloxifene are characterized by a large number of extraskeletal effects that have to be taken into account when counseling postmenopausal women on the use of these agents for the prevention or treatment of osteoporosis.

Osteoporosis due to steroid therapy is one of the most frequent and serious adverse events of antirheumatic therapy. The greatest loss of bone occurs during the 1st year of steroid intake, with the largest loss in the spine. Up to 50% of the patients, mostly postmenopausal women, suffer vertebral fractures. The prevalence of osteoporosis in 60-year-old patients with rheumatoid arthritis (RA) is more than double compared to the normal population. There are more risk factors other than age, gender, and menopause. Independent from the underlying disease, glucocorticoid therapy is associated with a high risk of osteoporosis development. Among the clinical manifestations of osteoporosis, fractures of the vertebrae, hips, and ribs are the most common. In clinical practice, bone density measurements are mostly performed with the dual-energy X-ray absorptiometry (DXA) technique. Since prevalent vertebral fractures are strongly predictive of new fractures, X-rays of the lumbar and thoracic spine are indicated in patients who are scheduled to receive steroid therapy for > 3 months. The value of serologic bone markers has not yet been clearly established. On the basis of these risks and the high prevalence of already manifest osteoporosis, there is a clear indication for osteoprotective therapy in RA. Bisphosphonates and active vitamin D metabolites play an important role for therapy and prophylaxis of steroid-induced osteoporosis. In rheumatology it is often necessary to administer bisphosphonates intravenously due to the disability of the patients. The clear necessity for prophylaxis and therapy of steroid-induced osteoporosis must be stressed. Efforts should be intensified to ensure even more consistent application in daily practice. Doctors should treat their steroid patients on the basis of the clear-cut indications for intervention despite budget problems.

Isoprene is the main component of steroid hormones. It is found in many plants and herbal compounds, e.g. the isoflavonoids are therefore slightly estrogenic. Since they are bound to the estradiol receptors, more active estrogens cannot induce a signal transduction. Hence phytoestrogens may be protective on breast tissue and other hormone dependent organs.