Generalized Bone Disease Research Articles

Prevention and treatment of osteoporosis

Osteoporosis is a generalized bone disease characterized by diminished bone strength with an increased risk of fractures. Osteoporosis is a major health concern, both because of the risk of potentially serious fractures and because its prevalence is increasing as the population ages. The treatment of the disease is complex and includes adherence to a particular diet, medications (hormone replacement therapy, calcium, vitamin D, etc.), kinesitherapy, physiotherapy and orthotics. To reduce osteoporosis, it is necessary to avoid the risk of fractures, to do regular physical activities, to eat bone-healthy foods, to lead a proper lifestyle with the avoidance of negative habits and to maintain a healthy weight. A person also needs to have knowledge of personal risk factors and to consult a doctor if medical treatment is to be applied. The classic therapeutic approach is with antiresorptive anti-osteoporosis agents. A promising therapeutic trend is the study of compounds with low toxicity and potential properties to influence the pathogenetic mechanisms of disease and oxidative stress, such as phytoestrogens and hormone replacement therapy, at the same time. The aim of the article is to familiarize the audience with the preventive measures and therapies applied to the treatment of osteoporosis.

An Autopsy Based Study of Sexual Dimorphism of Adult Human Sterna

Creation of an individual’s biological profile is of extreme importance and depends on age, sex and stature. The cranial and pelvic bones are important in identifying the sex of an individual. However, loss of complete bones or bones getting destroyed renders it impossible to use them for such estimations. However, since such sex-specific bones are hard to find at each and every scene, forensic experts are left with no choice but to depend on less sexually dimorphic elements of the human skeleton such as the sternum. This study was conducted in subjects that were subjected to medicolegal autopsy. The deceased aged 18 years and above, of either sex, were included in study. The deceased with evidence of trauma and surgery to the anterior chest wall, generalized bone diseases, observable deformities over the sternum were excluded. The analysis of 300 sterna was carried out to study sexual dimorphism in sternum using different parameters such as width of suprasternal notch, width of sternum at level of fourth rib, posterior curved length of sternum, manubrio-corpus index and length of sternum.

Polymorphism of bone morphogenetic protein (BMP2) and osteoporosis etiology

Osteoporosis is a chronic, generalized bone disease conditioned by many factors among which the genetic background plays the significant role. Bone morphogenetic protein (BMP2), a growth factor belong to su- perfamily of TNF- proteins, is actively involved in bone tissue metabolism. BMP2 protein shows the osteoinduction potential and regulates growth of cartilage plate, and the same directly influences the process of osteogenesis. The aim of study was to examine the frequency of genotypes and alleles of 570A>T and 5375G>A of BMP2 gene polymorphisms in population of Polish postmenopausal women, as well as to analyze the relationship between investigated polymorphic variants and bone turnover parameters. Into the study 117 postmenopausal women, Caucasian race (average age 55,1 years) living in Wielkopolska region were classified. The analysis of 570A>T and 5375G>A BMP2 polymorphisms was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) while bone mineral density (BMD) was measured by DEXA method. In the research the chosen clinical and bone turnover parameters were analysed. In both 570A>T and 5375G>A BMP2 polymorphisms the similar frequency of genotypes and alleles in investigated groups of postmenopausal women with osteoporosis, osteopenia and in the group with correct T-score were noted. The analysis do not show the relationship of clinical and bone turnover parameters with particular genotypes of BMP2 polymorphisms in women with osteoporosis, osteopenia and in the group with correct T-score. The research did not confirm directly relationship of 570A>T and 5375G>A BMP2 polymorphisms with osteoporosis development in population of Polish postmenopausal women. The investigation also shows lack of correlation of 570A>T and 5375G>A BMP2 polymorphisms polymorphisms with analysed clinical and bone turnover parameters.

Clinical aspects of primary hyperparathyroidism: clinical manifestations, diagnosis, and therapy

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia. An autonomous overproduction of parathyroid hormone leading to hypercalcemia, which is not downregulated by the calcium-sensing receptor, is the pathophysiological basis of the disease. The classical manifestations of PHPT include a generalized bone disease, kidney stones, and nephrocalcinosis, gastrointestinal, cardiovascular, neuromuscular and neuropsychiatric symptoms. Recently, the clinical presentation of PHPT, however, has changed in Western countries, it occurs oligo-asymptomatic in up to 80 %. Clinical examination, laboratory, and imaging techniques for the characterization of the disease and the localization include the diagnostic procedure. If possible, parathyroidectomy is the treatment of choice for clinically overt PHPT, for asymptomatic PHPT guidelines were developed in order to decide in individual cases between surgical and conservative approach; this consists of monitoring, adequate calcium and vitamin D intake, as well as hydration. Medical therapy includes bisphosphonates and calcimimetics.

AB0622 Significance of body mass index for the effect of bisphosphonate therapy in women with postmenopausal osteoporosis

BackgroundOsteoporosis is generalized bone disease characterized by disturbed bone strength, consequently fracture predisposition increases. One of the risk factors for osteoporotic fractures is the Body Mass Index (BMI) and it...

Aspectos óseos de la enfermedad de Gaucher

The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various “scores” to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.

Identification of differentially expressed genes in trabecular bone from the iliac crest of osteoarthritic patients

Osteoarthritis (OA) is clinically characterized by degeneration of the joints and has been traditionally considered a primary disorder of articular cartilage, with secondary changes in the subchondral bone. The increased bone mass and generalized changes in bone quality observed in osteoarthritic patients suggest that OA may be a primary systemic bone disorder with secondary articular cartilage damage. The iliac crest is a skeletal site distant from the affected joint, with a minimal load-bearing function. To provide evidence that OA is a systemic disorder, we searched for differentially expressed genes in the iliac crest bone of patients suffering from hip OA. Gene expression levels between bone samples collected at surgery from the iliac crest of patients undergoing total hip arthroplasty for primary OA and younger donors, who were undergoing spinal arthrodesis, were investigated by means of oligonucleotide microarrays. To verify data detected by microarrays technology, Real Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assays were performed with specimens from osteoarthritic patients and donors, as well as from elderly donors who were undergoing arthroplasty for subcapital femoral neck fracture. The microarray analysis surveyed 8327 genes and identified 83 whose expression levels differed at least 1.5-fold in the OA group (P<0.005). Comparisons between Real Time RT-PCR data from OA and the two donor groups indicated differential expression of genes involved in bone cell functions in the group of OA patients. The genes identified, including CCL2, FOS, PRSS11, DVL2, AKT1, CA2, BMP6, OMD, MMP2, TGFBR3, FLT1, BMP1 and TNFRS11B, have known roles in osteoblast or osteoclast activities. The data from this study identify a set of genes, closely related to bone cell functions, in which differential regulation in osteoarthritic bone distant from the diseased subchondral bone might underlie the etiopathogenesis of OA as a generalized bone disease.

Concordance of a Self Assessment Tool and Measurement of Bone Mineral Density in Identifying the Risk of Osteoporosis in Elderly Taiwanese Women

Objective Osteoporosis is the most common generalized bone disease related to aging. The Osteoporosis Self-Assessment Tool for Asians (OSTA) risk index was developed to screen postmenopausal Asian women to identify women who should be evaluated with bone densitometry. In Taiwan, there is no report of the validity of the OSTA with dual energy X-ray absorptiometry (DXA) as a reference. In this study, we assessed the validity of the OSTA risk index and discuss its applications, using DXA of the lumbar spine as the gold standard. Patients and Methods Healthy subjects, aged 30–85 years, who were receiving a health check-up at a teaching hospital in eastern Taiwan were invited to participate in this study. All subjects gave their consent to analyze their data. A self-administered questionnaire was used to assess their demographic characteristics, and reproductive and medical histories. Bone mineral density of the posterior-anterior lumbar spine was measured by DXA, and a diagnosis of osteoporosis was made according to World Health Organization criteria. The sensitivity and specificity and their 95% confidence intervals (CIs) were calculated for the dichotomized OSTA risk index. Results This cohort consisted of 498 postmenopausal Taiwanese women, with a mean age of 60.3 ± 7.6 years and a mean weight of 57.9 ± 8.9 kg. Spinal DXA revealed that 35.9% were osteoporotic (with a T-score of £ −2.5). The OSTA risk index at the standard cut-off point of £ −1 had a sensitivity of 57.0% (95% CI: 52.7, 61.3) and a specificity of 69.3% (95% CI: 65.3, 73.4). Among women aged 60–70 years, the sensitivity, specificity, and accuracy of the OSTA risk index were 77.1% (95% CI: 63.7, 76.9), 49.2% (95% CI: 42.0, 56.4), and 64.9% (95% CI: 60.7, 69.8), respectively. Conclusion The OSTA risk index is a convenient but not a very sensitive tool to help target high-risk women aged 60–70 years for DXA testing. Clinical risk factors and the OSTA risk index should be combined to assess women aged £ 60 years. Further study of the validity of the OSTA risk index among elderly women with a larger sample size in different populations should be conducted with spinal and femur neck DXA testing as references.

Shwachman–Diamond syndrome is associated with low-turnover osteoporosis

Introduction Shwachman–Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow dysfunction. These result in malabsorption and hematological abnormalities. A skeletal dysplasia is also an integral feature of SDS. The present study assessed prevalence and determinants of osteopenia and osteoporosis in patients with SDS and disease-causing mutations in the SBDS gene. Materials and methods Eleven patients (8 males) aged from 5 to 37 years (median 16.7 years) with a genetically confirmed diagnosis of SDS were assessed for fracture history, bone mineral content (BMC), lean tissue mass (LTM) and bone mineral density (BMD) (Hologic Discovery A), osteoporotic vertebral changes, and for blood biochemistry and hematological parameters. Iliac crest bone biopsies were obtained from four patients for histology and histomorphometry. Results The main findings were: (1) markedly reduced BMD Z-scores at the lumbar spine (median − 2.1, range − 4.4 to − 0.8), proximal femur (median − 1.3, range − 2.2 to − 0.7) and, whole body (median − 1.0, range − 2.8 to + 0.6), and reduced Z-scores for height-adjusted BMC/LTM ratio (median − 0.9, range − 3.6 to + 1.1); (2) vertebral compression fractures in three patients; and (3) blood biochemistry suggestive of mild vitamin D and vitamin K deficiency. Bone biopsies in four patients showed significant low-turnover osteoporosis with reduced trabecular bone volume, low numbers of osteoclasts and osteoblasts, and reduced amount of osteoid. Conclusions The results suggest that in addition to the skeletal dysplasia, SDS is associated with a more generalized bone disease characterized by low bone mass, low bone turnover and by vertebral fragility fractures. Osteoporosis may result from a primary defect in bone metabolism, and could be related to the bone marrow dysfunction and neutropenia.

Odnos indeksa tjelesne mase i mineralne gustine kosti kod žena u postmenopauzi

Osteoporosis is a generalized bone disease, characterized by a disturbed bone strength, thus the fractures occur more often. Persons with osteoporosis should be actively searched for in the population of postmenopausal women. Significant risk factors in the women in the post-menopause are lack of estrogen and small body mass index (BMI) (<19 kg/m2). The aim of the study was to examine the correlation between the BMI value and mineral bone density (MBD) in postmenopausal women. The study encompassed 100 postmenopausal women, from 46 to 70 years o age (59.08±6.07 years). All the examinees have their body mass measured and height and the respective BMI was calculated, and the MBD was densitometrically determined, by means of two-energy absorptionmetry of the X-rays. MBD was measured on the central skeleton (lumbar spine and both hips). According to the densitometrical findings, the criterion for osteoporosis was T sum lower than -2.5 SD. The values of BMI were respectively compared to the values of the total T sum of the lumbar spine and both hips, and the values of the T sum of the spine and hip. The results have shown that 18% of the examinees had a normal body mass, 1st level of obesity was found in 52%, 2nd level of obesity in 25%, and 3rd level of obesity was found in 7% of the examinees. Average value of BMI in the examinees was 28.27±4.12 kg/m2. Average value of the total T sum of the lumbar spine was -2.19 SD±1.25, and T sum of the hip was -1.11 SD±0.95. It was established a statistically significant positive correlation (r=0.01) between the BMI and MBD of the hip, while between BMI and MBD of the lumbar spine there wasnot any. There was a statistically significant correlation between the lumbar spine and hip MBD values (r=0.01). BMI is well-known and significant predictor of MBD of the entire skeleton. In the postmenopausal women, BMI is more significant as the MBD of the hip than of the spine. MBD on the hip increases with the body mass and height increase in postmenopausal women, due to a significant fat tissue that produces leptin and other bioactive peptides, which play a protective role in the bone development. Nonexistence of the spine BMI and MBD correlation in postmenopausal women could possibly be caused, above all, by the lack of estrogen and a faster bone metabolism in the spinal area.

Pathologic Quiz Case: Hepatosplenomegaly in an Infant With Hypotonia and Coarse Facial Features

Pathologic Quiz Case: Hepatosplenomegaly in an Infant With Hypotonia and Coarse Facial Features

Diabetes mellitus a risk for osteoporosis?

Localized lesions at the foot skeleton are a serious and well recognized complication of diabetes mellitus which may impair the clinical outcome of the patients remarkably. In contrast, the presence of a generalized bone disease or osteoporosis related to diabetes mellitus is less acknowledged and its clinical relevance is less obvious. This paper is a clinically focused review of the literature on osteoporosis related to diabetes mellitus. Due to the different pathogenesis of diabetes mellitus type 1 and type 2 it is not surprising that there is no uniform entity of diabetic osteopathy. The majority of clinical studies in subjects with diabetes mellitus type 1 showed a moderately decreased bone mass at the forearm, while bone mass at the femur or lumbar spine was either decreased or not different from non-diabetic controls. In patients with diabetes mellitus type 2 the risk of osteopenia is not as clear as in type 1 diabetes. Bone mineral density at the forearm in patients with type 2 diabetes mellitus was decreased, unchanged or even increased in comparison to controls, while bone mineral density at the vertebrae or femoral neck was either not significantly different or increased, but rarely decreased. The underlying mechanisms triggering changes in bone mass in patients with diabetes mellitus type 1 and type 2 are not well known. In most studies there was no consistent relationship between the metabolic control of diabetes and bone mineral density. Biochemical parameters of the calcium and bone metabolism showed no clear relationship to the bone mineral density measurements. From few bone histology studies in humans and experimental studies there is evidence that a decreased bone formation is one major mechanism leading to reduced bone mass in diabetics. Microangiopathy at the bone tissue was also discussed as a possible reason for diabetic osteopenia. It was shown that insulin and insulin like growth factors (IGF-1, IGF-2) have an influence on bone metabolism itself and other growth factors, cytokines and hormones may determine changes in diabetic bone metabolism. Recent findings suggest that leptin is involved in the regulation of osteoblast function and bone mass, which is of special interest in diabetes mellitus type 2. The clinical relevance of osteoporosis or osteopenia is determined by the increased risk for insufficiency fractures. Few studies found an increased fracture risk, especially in older women with type 1 diabetes mellitus, while others did not show an increased risk for fractures or even found a decreased rate of fractures in women with diabetes mellitus type 2. There is a need for further longitudinal studies, including the incidence and risk factors for osteoporotic fractures. In clinical routine the extent of diagnostic and therapeutic activities in patients with type 1 or type 2 diabetes mellitus in respect to generalized bone disease or diabetic osteopenia should be based on individual conditions and risk profile for osteoporosis.

Child Abuse in Saudi Arabia: Report of Ten Cases

Ten abused children under five years of age (four males, six females) were seen in King Faisal Specialist Hospital and Research Centre (KFSH&RC) between 1989G and 1992G. Two children died, five had serious injuries and three had moderately severe injuries. In one of the fatalities, the diagnosis was not suspected until four years after death, when her sister was diagnosed as a case of child abuse. Six children suffered varying degrees of physical neglect and abuse and sexual abuse. The remaining four children had Munchausen syndrome by proxy. Parentally induced illness should therefore be considered in the differential diagnosis of unusual illness with bizarre features, even if the parents' behavior appears normal.

Periphere quantitative Computertomographie zur Knochenmineralmessung mit einem neuen speziellen QCT-Scanner

Some years ago we designed a special purpose gamma-ray QCT scanner for bone mineral measurements at the forearm. Currently, the first commercially built scanners (Stratec SCT 900) are being tested and clinically evaluated. The scanner uses an 125I photon source with a multidetector translate rotate fan beam geometry and newly developed semiconductor crystals. Quantification of trabecular bone and total bone at a standardized radial cross section gives an in-vivo reproducibility of less than 1%, which is superior compared to all other bone mineral measurement techniques. In-vitro reproducibility is between 0.2 and 0.4%, measured with calibration phantoms. The high in vivo reproducibility is ensured by automatic contour finding algorithms to determine the bone mass within a forearm cross sectional slice. A number of healthy men (n = 201) and women (n = 400) were examined to obtain a reference population for comparison to patients with generalized bone disease. We compared 182 osteoporotic females with healthy subjects. The high precision of the device and the high sensitivity of the measurement site considering changes of trabecular bone mass provide a very powerful means for monitoring bone mineral loss or changes due to therapy, as well as high diagnostic sensitivity.

Physical and histomorphological characteristics of iliac crest bone differ according to the grade of osteoarthritis at the hand

The amount of cortical and trabecular bone was studied in 32 iliac crest necropsy specimens from women 60–75 years of age and examined according to the grade of osteoarthritis. Three different methods to evaluate bone mass were used: dual photon absorptiometry, physical assessment according to Archimedes' principle, and histomorphometry. Patients were divided into groups—with or without osteoarthritis—according to the presence of osteoarthritis on hand x rays. A significantly increased amount of cortical and trabecular bone mass was found in those who had osteoarthritis at the hands. Percent pure/crude bone volume and trabecular width were found to be increased with osteoarthritic grade, indicating that primary osteoarthritis is probably part of a generalized bone disease.

Comparison of bone mass measured by histomorphometry on iliac biopsy and by dual photon absorptiometry of the lumbar spine

In a prospective study we compared bone mass measured independently by dual photon absorptiometry (DPA) on lumbar spine and by histomorphometry on transiliac biopsy. Measurements were done in 83 patients (23 males, 60 females) with various generalized bone diseases, including spinal osteoporosis, primary hyperparathyroidism and osteopetrosis. Iliac bone density was analyzed on bone biopsy with an automatic image analyzer and expressed as the trabecular bone volume (TBV), the cortical thickness (CT) and the total bone density (TBD) which includes the density of both spongy and cortical bone within the periosteal envelope. The bone mineral content (BMC) and density (BMD) were measured from L 2 to L 4 with a Novo Lab 22a device. For the 83 patients, there were significant correlations between values given by both methods, with r values ranging from 0.74 to 0.43, according to the bone mass parameters analyzed. In the 37 patients with untreated vertebral osteoporosis, the TBV—but not the CT nor the TBD—correlated significantly with the BMD of the spine ( r = 0.53, p < 0.001). In conclusion, there is a significant correlation between bone density of the iliac crest assessed histomorphometrically and spinal density measured by DPA. Despite the fact that DPA measures both trabecular and cortical bone of the spine, it correlates better with iliac trabecular bone mass than with the overall iliac bone density.

Collagen and Non-Collagenous Protein Content (Osteocalcin, Sialoprotein, Proteoglycan) in the Iliac Crest Bone and Serum Osteocalcin in Women with and without Hand Osteoarthritis

Quantitative and qualitative variations in bone composition were studied in postmortem iliac crest bone specimens from 32 women aged 60 to 75, grouped according to the presence of osteoarthritis at the hand joints. The EDTA extraction yield of macromolecules was significantly greater in the osteoarthritis group. Collagen and osteocalcin content were significantly increased and proteoglycan content decreased in the osteoarthritis group. No difference in sialoprotein content was found.In a clinical study of 20 patients with generalised osteoarthritis, we found compared to 15 controls also significantly increased serum levels of osteocalcin.These results indicate in an unselected group of cases that differences in bone matrix constituents exist between elderly women with and without an osteoarthritic constitution. The finding that these alterations are present even far away from the articular lesion, and the fact that the serum osteocalcin levels are elevated, indicate that osteoarthritis is part of a more generalised bone disease and not a purely cartilage disease.

Noninvasive bone mineral measurements

Single and dual photon absorptiometry are now available to aid the physician in diagnosis and management of generalized bone diseases. Both methods are reviewed in detail. They allow an accurate and reproducible assessment of bone mineral at predominantly cortical (appendicular skeleton) and trabecular (axial skeleton) bone sites. Newer findings show that cortical and trabecular bone behave differently and that the effect of endocrine dysfunction on bone appears to be both disease and site specific. These qualitative and quantitative differences in cortical and trabecular bone loss require that an optimal sampling site has to be found for a given bone problem if maximum benefit is to be derived from these tests.

The diagnostic value of the alveolar lamina dura in generalised bone disease (author's transl)

Changes in the alveolar lamina dura in 134 patients have been analysed. They included 32 cases with urolithiasis in whom generalised bone disease had been excluded, 37 cases of primary hyperparathyroidism, 31 cases of secondary hyperparathyroidism and 34 with primary osteoporosis. The state of the lamina dura was related to biochemical, radiological and histological findings in the various groups. The value of the lamina dura in the diagnosis of generalised skeletal abnormalities has been defined.

Metaphyseal fractures in osteogenesis imperfecta.

Forty-one children with osteogenesis imperfecta have been reviewed. A minority (7/41) showed small metaphyseal fractures, resembling those seen in non-accidental injury, but in all of these there was obvious generalized bone disease so that confusion with non-accidental injury did not occur.