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Definition and Epidemiology: Chronic kidney disease (CKD): abnormalities of kidney structure or function, present for over 3 months. Staging of CKD is based on GFR and albuminuria (not graded). Osteoporosis: compromised bone strength (low bone mass, disturbance of microarchitecture) predisposing to fracture. By definition, osteoporosis is diagnosed if the bone mineral density T‑score is ≤ -2.5. Furthermore, osteoporosis is diagnosed if a low-trauma (inadequate trauma) fracture occurs, irrespective of the measured T‑score (not graded). The prevalence of osteoporosis, osteoporotic fractures and CKD is increasing worldwide (not graded). PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD): Definition of CKD-MBD: a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; renal osteodystrophy; vascular calcification (not graded). Increased, normal or decreased bone turnover can be found in renal osteodystrophy (not graded). Depending on CKD stage, routine monitoring of calcium, phosphorus, alkaline phosphatase, PTH and 25-OH-vitamin D is recommended (2C). Recommendations for treatment of CKD-MBD: Avoid hypercalcemia (1C). In cases of hyperphosphatemia, lower phosphorus towards normal range (2C). Keep PTH within or slightly above normal range (2D). Vitamin D deficiency should be avoided and treated when diagnosed (1C)., Diagnosis and Risk Stratification of Osteoporosis in Ckd: Densitometry (using dual X‑ray absorptiometry, DXA): low T‑score correlates with increased fracture risk across all stages of CKD (not graded). A decrease of the T‑score by 1 unit approximately doubles the risk for osteoporotic fracture (not graded). A T-score ≥ -2.5 does not exclude osteoporosis (not graded). Bone mineral density of the lumbar spine measured by DXA can be increased and therefore should not be used for the diagnosis or monitoring of osteoporosis in the presence of aortic calcification, osteophytes or vertebral fracture (not graded). FRAX can be used to aid fracture risk estimation in all stages of CKD (1C). Bone turnover markers can be measured in individual cases to monitor treatment (2D). Bone biopsy may be considered in individual cases, especially in patients with CKD G5 (eGFR < 15 ml/min/1.73 m 2 ) or CKD 5D (dialysis)., Specific Treatment of Osteoporosis in Patients With Ckd: Hypocalcemia should be treated and serum calcium normalized before initiating osteoporosis therapy (1C). CKD G1-G2 (eGFR ≥ 60 ml/min/1.73 m 2 ): treat osteoporosis as recommended for the general population (1A). CKD G3-G5D (eGFR < 60 ml/min/1.73 m 2 to dialysis): treat CKD-MBD first before initiating osteoporosis treatment (2C). CKD G3 (eGFR 30-59 ml/min/1.73 m 2 ) with PTH within normal limits and osteoporotic fracture and/or high fracture risk according to FRAX: treat osteoporosis as recommended for the general population (2B). CKD G4-5 (eGFR < 30 ml/min/1.73 m 2 ) with osteoporotic fracture (secondary prevention): Individualized treatment of osteoporosis is recommended (2C). CKD G4-5 (eGFR < 30 ml/min/1.73 m 2 ) and high fracture risk (e.g. FRAX score > 20% for a major osteoporotic fracture or > 5% for hip fracture) but without prevalent osteoporotic fracture (primary prevention): treatment of osteoporosis may be considered and initiated individually (2D). CKD G4-5D (eGFR < 30 ml/min/1.73 m 2 to dialysis): Calcium should be measured 1-2 weeks after initiation of antiresorptive therapy (1C)., Physical Medicine and Rehabilitation: Resistance training prioritizing major muscle groups thrice weekly (1B). Aerobic exercise training for 40 min four times per week (1B). Coordination and balance exercises thrice weekly (1B). Flexibility exercise 3-7 times per week (1B)., (© 2022. The Author(s).)

A Distal Radius Fracture Is Not Simply a Distal Radius Fracture Abstract. We report on a 57-year-old female patient with a distal extra-articular radius fracture. The family doctor's suspicion was an osteoporosis-associated fracture, and an interdisciplinary investigation was initiated. In addition to DXA measurement differential diagnoses for secondary osteoporosis were considered. In our case, secondary osteoporosis was diagnosed as part of Graves' disease and insufficiency of vitamin D leading to a radius fracture.

Testosterone is a natural hormone which is essential to maintaining physical and emotional wellbeing in men, regardless of age. Male hypogonadism is an endocrine condition of testosterone deficiency with the potential to cause multiple morbidities and psychosocial problems. The condition can be of primary (testicular), secondary (hypothalamic-pituitary) or so-called functional origin (as a result of inflammatory conditions, obesity or chronic illness). Testosterone deficiency can cause symptoms of a sexual nature, foster metabolic dysfunction and impair physical abilities as well as cause osteopenia/osteoporosis and anemia. Testosterone replacement therapy should not be initiated in the case of desired paternity, unclear processes of the prostate or mammary gland and high hematocrit. Diagnosis and treatment as well as monitoring of hypogonadism treatment are clearly regulated by international guidelines and replacement therapy is proven to be effective in ameliorating the above-mentioned symptoms when performed according to these guidelines. In functional hypogonadism, which is most often, but not exclusively, found in older men, treatment of the underlying condition/co-morbidity is mandatory prior to starting testosterone substitution.

Thyroid hormones are key regulators of skeletal development in childhood and bone homeostasis in adulthood, and thyroid diseases have been associated with increased osteoporotic fractures. Hypothyroidism in children leads to an impaired skeletal maturation and mineralization, but an adequate and timely substitution with thyroid hormones stimulates bone growth. Conversely, hyperthyroidism at a young age accelerates skeletal development, but may also cause short stature because of a premature fusion of the growth plates. Hypothyroidism in adults causes an increase in the duration of the remodeling cycle and, thus, leads to low bone turnover and enhanced mineralization, but an association with a higher fracture risk is less well established. In adults, a surplus of thyroid hormones enhances bone turnover, mostly due to an increased bone resorption driven by osteoclasts. Thus, hyperthyroidism is a well-recognized cause of high-bone turnover secondary osteoporosis, resulting in an increased susceptibility to fragility fractures. Subclinical hyperthyroidism, especially resulting from endogenous disease, also has an adverse effect on bone mineral density and is associated with fractures. In most patients with overt or subclinical hyperthyroidism restoration of the euthyroid status reverses bone loss. In postmenopausal women who receive thyroid-stimulating hormone suppression therapy because of thyroid cancer, antiresorptive treatments may be indicated. Overall, extensive data support the importance of a euthyroid status for bone mineral accrual and growth in childhood as well as maintenance of bone health in adulthood.

Osteoporosis is defined as a systemic bone disease with decreased bone strength and an increased susceptibility for fractures. Older people in particular face an increased risk of fractures. These kind of fractures are usually caused by an inadequate trauma and are the so-called fragility fractures. In older adults immediate fracture stabilization and early mobilization have become the standard procedure after a fragility fracture. Treatment of the underlying osteoporosis often plays a minor role in clinical practice. Only a small group of patients are already under osteoporosis medication and even after a fracture occurs only few patients receive osteoporosis drug treatment with the aim to reduce the progression of osteoporosis and to reduce subsequent fractures. In the literature this has been described as the osteoporosis care gap. The following article presents an overview of treatment options and answers many different questions from the clinical routine.

Through a more consistent diagnostics and treatment of osteoporosis, subsequent fractures and associated complications could be reduced in aged patients. Whereas anticoagulants are now standard in the treatment of fractures of the lower extremities to prevent thromboembolic complications in orthopedic surgery and an omission of anticoagulation can be regarded as medical malpractice, the management of osteoporosis following such fractures is very frequently disregarded. Although guidelines for osteoporosis, such as those from the governing body on osteology (Dachverband Osteologie, DVO) from 2014 are not legally binding as such, the breach of this standard of care can constitute a breach of medical obligation by the physician. The omission of osteoporosis diagnostics and initiation of treatment despite appropriate findings after fractures in aged patients, could represent a diagnostic assessment error and severe malpractice in the legal sense. In this case, evidence of a serious malpractice could be associated with civil, criminal and professional claims which could be linked with relevant legal consequences. Regardless of the legal consequences for omission of osteoporosis management following multiple fractures in aged patients, the management of osteoporosis should be an integral component in the treatment of these patients in the future.

Rheumatic diseases in childhood and adolescence can lead to secondary osteoporosis based on various pathophysiologies. The underlying disease, medication and immobility resulting in a reduced osteoanabolic stimulus contribute to the development of a fragile skeletal system. For diagnostic purposes dual-energy X-ray absorptiometry (DXA) is the most frequently used technology. For interpretation of the areal bone mineral density, age and gender matched reference data have to be used. Particularly in the pediatric field, body height must additionally be taken into consideration. Further techniques which can provide detailed information are peripheral quantitative computed tomography and high resolution magnetic resonance imaging. Nowadays, skeletal assessments have to be interpreted in the context of the muscular system. The concept of the functional muscle-bone unit is widely accepted and uses the muscles as the dominating factor. In a second step the adaptation of the skeletal system to the applied muscle force is evaluated. This allows a differentiation between primary and secondary skeletal diseases depending on the ratio of muscles to bone. Therapeutic options for secondary osteoporosis include reduction of the causative medication, treatment of the underlying disease, antiresorptive treatment with bisphosphonates and different programs to activate the muscles. A multimodal interval rehabilitation program including alternating side vibration shows positive effects on mobility, muscle function and bone mass in children and adolescents.

Disturbances in bone and mineral turnover are common complications in patients with impaired renal function. Besides an increased risk for cardiovascular events they promote skeletal events, such as bone pain and fractures. Evidence for the antifracture efficacy of antiresorptive and osteoanabolic treatment strategies has only been demonstrated for patients with osteoporosis. The use of osteotropic drugs in patients with impaired renal function requires large randomized placebo-controlled trials.

Rheumatoid arthritis (RA) is a bone-destructive disease that is a serious risk factor for the development of osteoporosis, which is defined by a loss in bone quality and an increased fracture risk. The proinflammatory cytokines tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and IL-17, in particular, contribute to local and systemic bone loss in RA. While effectively reducing inflammation, glucocorticoids add to the fracture risk. Therefore, an adequate supply of calcium and vitamin D is essential. For many patients with RA, bone density measurements are recommended.

In a female Thuringian forest goat osteoporosis, dwarfism and anaemia were found. The animal was kept on a hobby farm with 30 further goats that did not show clinical signs. Radiological examination, computed tomographic imaging and pathological examination revealed reduced bone density and numerous fractures associated with limited or completely absent callus formation. Incineration of selected bones did not show any differences concerning the contents of calcium and phosphorus when compared to two control goats. Therefore, a regular mineralisation of the bone matrix was indicated. The dysfunction associated with the osteogenesis was assumed to be a copper deficiency.

Osteoporotic fractures are a frequent cause of functional disabilities and loss of quality of life. Preventive measurements need to focus on training of muscle function and coordination, and adequate daily calcium and vitamin D supplementation; furthermore a regular check up for drugs associated with falls and osteoporosis. The German guideline recommends that a specific osteoporosis medication should be initiated in individuals with a 10-year risk for hip and vertebral fractures of 30%. This article presents the current guideline for osteoporosis including the actual updates.

Medical treatment of patients with liver cirrhosis consists mainly of symptomatic therapy of associated complications. Apart from the classical complications of cirrhosis, e. g. ascites, portal hypertension or hepatic encephalopathy, other frequent complications are neglected in everyday medicine. The incidence of metabolic disturbances seems to be similar to the prevalence of classical complications of liver cirrhosis, such as portal hypertension or ascites. Osteoporosis is an important manifestation of hepatic osteopathy, especially in chronic cholestatic diseases and in candidates for liver transplantation, which necessitates timely adequate diagnostic test (e. g. osteodensitometry) and treatment (pre-emptive and causal). Malnutrition, especially when related to protein- and energy supply, is very common in patients with liver cirrhosis and has prognostic significance regarding mortality and complication rates. A sufficient daily energy and protein supply should be ensured, one which is higher than that for the normal population. Additional substitution of vitamins and trace elements is indicated when symptoms of deficiency became apparent., (Georg Thieme Verlag KG Stuttgart, New York.)

Osteoporotic fractures are a frequent cause of disability and a loss of quality of life in old age. Maintenance of muscle function and balance, a daily calcium intake of 1,000 mg, sufficient vitamin D, and a prudent use of fall- and osteoporosis-associated drugs are key components of fracture prevention. The German guideline recommends to initiate a specific long-term osteoporosis medication in individuals with a 30% 10-year risk for hip fractures and vertebral fractures.

The diagnostic approach to osteoporosis usually involves an ample risk assessment, a physical examination, a radiograph of the thoracic and lumbar spine, a bone densitometry using dual X-ray absorptiometry, and a basic blood test. The aim of this approach is to assign a person to one of the WHO-based diagnostic categories, and to estimate the ten-year fracture risk of this individual. In countries where available, the individual ten-year fracture risk can now easily be calculated for men and women of forty years of age and above, by using a computer-driven calculation tool, called FRAX, which has been developed by WHO recently.

Case Report: A 28-year-old woman was referred to hospital with a spontaneous femoral neck fracture. Dual energy X-ray absorptiometry showed severe osteoporosis without apparent cause or risk factors. The basic endocrinologic evaluation revealed hypercortisolism, and the diagnosis of Cushing's disease could be made following biochemical test and magnetic resonance imaging. A transsphenoidal resection of the pituitary gland tumor was performed and led to a cure of the disease. The patient received calcium and vitamin D substitution as well as biphosphonates., Conclusion: Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Only few cases with occult endogenous Cushing's syndrome and osteoporosis as the main manifestation of the disease have been reported. Nevertheless, hypercortisolism should be excluded whenever osteoporosis without apparent cause is diagnosed.

Osteoporosis and osteomalacia are systemic metabolic bone diseases characterized by an impaired composition, architecture, and quality of bone. In light of the demographic development and the recent use of sensitive tests, both diseases are increasingly diagnosed. Subjects at high risk include elderly, chronically hospitalized patients, and nursing home residents. Patients with gastrointestinal, rheumatologic and endocrine disorders are also at risk for the development of osteoporosis or osteomalacia. In this review, we will discuss practical aspects of the clinical presentation and the diagnosis of osteoporosis and osteomalacia.

Treatment of osteoporosis aims to reduce osteoporotic fractures and to minimize fracture-related pain and functional impairment. Components of non-drug therapy include improvement of muscle strength and coordination, treatment of modifiable causes of falls, a diet rich in calcium and sufficient in calories, adequate supply of vitamin D and an individual assessment of drugs known to increase falls or osteoporosis. Bisphosphonates, raloxifene, strontium ranelate and parathyroid hormone have been shown to reduce osteoporotic fractures in postmenopausal women. Alendronate, risedronate and parathyroid hormone are also licensed for the treatment of male osteoporosis. One of the still open questions is the optimal duration of pharmacological treatment.

Osteoporosis is a multifactorial disease entailing a high risk to sustain fragility fractures. Its susceptibility is determined by genetic and environmental factors and underlying diseases. Bone is rebuilt and regenerated by osteoclasts, osteoblasts and osteocytes. Local and systemic growth and differentiation factors such as Insulin-like growth factors, bone morphogenetic proteins and wnt-proteins confer anabolic signals, while the RANK/RANK-Ligand and Osteoprotegerin (OPG) system regulates bone resorption. The ratio of osteoclast stimulating RANKL and its soluble decoy receptor OPG is modulated by sex hormones, vitamin D, parathyroid hormone, local growth factors and mechanical loading. Osteocytes regulate bone mass via the bone formation inhibitor sclerostin. Bone is tightly interconnected with and regulated by the calcium/phosphate/vitamin D system via the parathyroid gland, the gut, liver and kidneys. Sex hormones are important for bone formation during adolescence and their loss in menopause/andropause exaggerates bone resorption. Basically over-activity of osteoclasts and/or functional deficits of osteoblasts can cause negative bone balance and favor osteoporosis.

Osteoporosis affects approximately 7 million patients in Germany and severely impairs quality of life. The clinical picture, subjective complaints as well as the presence or absence of risk factors are essential to determine the individual risk profile and to decide on possible serum blood tests, osteodensitometry, and X-ray examinations. Back pain or other clinical evidence of impaired bone stability should be evaluated with X-ray studies of the spine. If osteoporosis and an increased risk of fracture are present, treatment is indicated which includes an evidence-based pharmaceutical regimen in order to increase bone stability and to lower the risk of fractures. Drug treatment with adequate calcium and vitamin D supplementation and antiresorptive or osteoanabolic substances, usually for 3-5 years, should be accompanied by pain medication and neuromuscular rehabilitation to help prevent falls and maintain independence of the elderly.

Osteoporosis is a systemic disease of the bones with increasing incidence in the elderly. Over the age of 50 years bone mineral density continuously decreases resulting in osteoporotic fracture. Osteoporosis is positively correlated with late-onset hypogonadism and increases under androgen deprivation therapy. The evaluation of osteoporosis should be done in cooperation with an endocrinologist. Measurement of bone mineral density is recommended before starting androgen deprivation therapy. Patients with fracture and/or decreased bone mineral density 2.5 or more standard deviations below normal peak bone mass of young men should be treated. The appropriate treatment is calcium and vitamin D substitution combined with oral or i.v. administration of bisphosphonates.

Bisphosphonates have a set place in the treatment of osteoporosis in adults. For the last 10 years they have also been used in pediatrics. Due to inhibition in differentiation and reduction in osteoclasts, both pamidronate and alendronate, the most commonly used preparations, cause an increase in bone density. Most experience comes from the i.v. treatment of forms with severe courses of osteogenesis imperfecta (OI). There is an increase in bone substance, a decrease in rate of fractures and a reduction in pain with higher mobility of those effected. In addition to the use of drugs, intramedullary nailing and physiotherapy are important therapeutic standards. Bisphosphonates are also used for other diseases involving bone remodeling, such as juvenile idiopathic osteoporosis or familial hyperphosphatemia. Acute side effects usually occur with the first infusion, involve "flu-like" symptoms and are self limiting. The question of long-term side effects cannot be answered with the currently available data.

Bisphosphonates are potent inhibitors of bone resorption and approved agents for both the prevention and treatment of osteoporosis. Many clinical studies have shown a consistent reduction in the risk of vertebral fractures with the use of these drugs, while others have shown a clear reduction in the risk of hip and other non-vertebral fractures. The bisphosphonates are divided into three generations based on their potency and chemical structure. In general, as a substance group they are well tolerated and, when applied correctly, the toxicity is low. Alternative dosages, e.g. monthly, three times a month or yearly as an oral drug or i.v. would probably improve patient compliance. Clinical studies have also shown the safety and effectiveness of bisphosphonates over a period of 3-7 years.

According to the recently published BoneEVA study, 7.8 million Germans (6.5 million women) are affected by osteoporosis. Of them, 4.3% experienced at least one clinical fracture. Only 21.7% were treated with an anti-osteoporotic drug, whereby only 10% received a bisphosphonate and 17% given calcium and vitamin D. On the other hand, as osteoporosis may be associated with severe pain in 90% of patients, analgesics are prescribed. The total direct costs attributable to osteoporosis amounted to Euro 5.4 billion in 2003. One out of three postmenopausal women and one out of five men over the age of 50 years will experience osteoporotic fractures unless preventive measures are undertaken. According to the German guidelines for diagnosis and treatment of osteoporosis, bone densitometry using dual energy x-ray absorptiometry (DXA) together with other clinical risk factors (previous low trauma fracture, use of nicotine, low body weight [BMI<20 kg/m2], immobilisation, and more than two falls during the last six months) are recommended for diagnosis. Using typical cases out of clinical practice, this article delineates frequent mistakes in the interpretation of DXA measurements. Furthermore, the present paper clarifies the role of classical x-rays, which still represent the predominant procedure for the identification of fractures and especially vertebral fractures. In comparison to x-rays, CT or MRI are more important in differential diagnosis of malignant disease and bone metastases. Essentially a reduction of vertebral height without evidence of central endplate fracture in postmenopausal women may be unrelated to osteoporosis. Quantitative morphometry should not be used alone for the assessment of vertebral fracture in clinical decision-making. Therefore, we recommend differential diagnosis of morphometric vertebral deformities by an expert reader to rule out deformities related to degenerative disease and norm variants of which we will present several examples to train the view of the reader.

Since nowadays liver diseases are being diagnosed more frequently than in former years, an increasing number of patients with skeletal alterations is detected. Predominant is osteoporosis with the feared complications of bone fractures. The measurement of bone mineral density enables us to differentiate between normal, osteopenic and osteoporotic conditions. Despite the great number of data available on bone disease we are still incapable to predict which patients with liver disease will develop osteoporosis or bone fractures and when. Treatment should focus on the prevention of development of osteoporosis and fractures and rather not on the treatment of complications. We are still lacking convincing long-term treatment studies with a sufficient number of patients who are well stratified.

The main changes in the updated DVO guideline 2006 on prevention, diagnosis and treatment of osteoporosis in postmenopausal women and in older men concern the evaluation of individual fracture risks and the selection of medicamentous therapy by means of new thresholds. A 30% risk of osteoporotic vertebral or hip fracture per decade is recommended as the threshold for implementation of pharmacological therapy. Evaluation of the individual absolute fracture risk is based on a combination of the results of densitometry at the lumbar spine and femur, age, gender, and other risk factors that are specifically associated with osteoporosis. Patient's mobility is assessed by carrying out special mobility tests. Further changes seen in the 2006 update of the DVO guideline are therapy proposals taking account of new pharmaceutical developments. New effective medications are rh-PTH (1-34), or teriparatide, strontium ranelate, and ibandronate (bisphosphonate) for monthly oral administration. Minimally invasive operative techniques for use in vertebral fractures in combination with medicamentous antiosteoporosis therapy are also included in the 2006 update of the DVO guideline. Thus, in the 2006 update of the DVO-guideline we have a practice-oriented 53 guideline that is adapted to individual fracture risk and gives recommendations on the prevention, diagnosis and treatment of osteoporosis.

Sacral insufficiency fractures are an easily overlooked injury of the elderly, leading to severe and debilitating lower back pain. Percutaneous vertebroplasty with polymethylmethacrylate (PMMA) has become the treatment of choice for painful osteoporotic vertebral compression fractures. This is mainly due to the excellent results in pain relief, combined with the low morbidity of the procedure and the possibility of performing it in an outpatient setting. This well known technique can be transferred to the treatment of sacral insufficiency fractures for which no active therapy is currently available. This so-called sacroplasty was first reported in 2002 in a single case report. Six other patients with this indication have been reported in the Anglo-American literature to date. This article is the first description of this technique in the German literature. It compromises the description of two typical cases highlighting the difficulties in diagnosis, surgical technique and possible complications. Both patients were treated successfully and showed dramatic pain relief within several hours.

The cells of the malignant clone of plasmacell myeloma have cytogenetic aberrations in a substantial number of cases. Many of these abnormal karyotypes are predictive for an unfavorable outcome. Gene mutations and abnormal gene expression, particularly of oncogenes and tumor suppressor genes, are often observed in myeloma cells. The cross talk between the myeloma cells and the bone marrow microenvironment plays an important role for growth and survival of the tumor cells. As a consequence of this cell-to-cell-interaction, several cytokines are secreted. The intracellular signaling, evoked by these cytokines, leads to continuous growth and proliferation and inhibition of apoptosis. Since these molecular pathways have been defined, many new targets for therapeutical interventions become obvious. Some molecules, directed against cytokines, are under early clinical investigation. Medicaments intervening in the cross talk between the myeloma cell and the bone marrow stroma as Thalidomide, Lenalidomide or Bortezomib are already available. Many of the myeloma patients suffer from bone disease. Some new drugs inhibiting the differentiation and activation of osteoclasts are evaluated in clinical trials. These molecules will be an important contribution against the painful bone disease of plasmacell myeloma.

History: Pronounced osteoporosis was discovered in a 44-year-old man presenting with an herniated intervertebral disk. He reported severe myopia, incomplete dislocation of the lenses and retinal detachment. He did not know of any thrombembolic events in the past. On physical examination Marfan-like appearance and a funnel chest were noted. Because of these findings Marfan syndrome was suspected., Investigations: Considering the findings of the x-rays, homocystinuria was suspected as a cause of osteoporosis, despite apparently normal cognitive functions. This diagnosis was confirmed by greatly increased values of serum homocysteine and a positive test for urinary homocystine. Since methionine and homocystine were both elevated, the diagnosis of cystathionin-beta-synthase deficiency was established., Diagnosis, Treatment and Course: After taking folate and vitamin B6, the homocysteine level decreased moderately. Betaine and subsequently vitamin B12 were added. Homocysteine values declined markedly on this therapeutic regimen. Two years later the patient was admitted again because of atypical angina. Coronary heart disease could be excluded by coronary angiography., Conclusion: Diagnosis of premature osteoporosis should prompt consideration of homocystinuria even in adults. Premature arteriosclerosis, thrombembolic diseases, dislocation of the lens and retinal detachment may give further clues.