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PubMed1995

Osteoporosis.

Two complementary notions need to be considered in the definition of osteoporosis: a reduction in bone mineral density and the occurrence of fracture. Bone mineral density is an established determinant of the risk of future fracture, but current interventions are most usefully targeted before bone density has fallen to the levels at which fractures usually occur. Bone density may now be measured accurately and precisely, and the sensitivity and specificity of this technology for fracture risk prediction are high. It therefore seems reasonable to classify osteoporosis in terms of both a reduction in bone density and the occurrence of fracture. On this basis, a four point scale has recently been proposed by the World Health Organization: 1) normal, 2) low bone mass, 3) osteoporosis and 4) established osteoporosis. While it is likely that this diagnostic classification will change as experience of osteoporosis increases, it is important to have widely adopted guidelines of this type which act as a framework for further research.

Humans↗

PubMed1997

How do we manage specific types of osteoporosis?

Osteoporosis in children, adolescents and corticosteroid-treated patients represent a particular problem for clinicians. In children and adolescents, the main management question is whether any specific interventions can influence attainment of peak bone mass and so decrease the chance of osteoporosis in later adult life. The role of physical activity and calcium in particular are reviewed. In adolescence, osteoporosis is usually due to idiopathic juvenile osteoporosis or secondary to amenorrhoea or anorexia nervosa. These entities, as well as the management of corticosteroid-induced osteoporosis at all ages, are discussed.

Adolescent↗

PubMed1999

Osteoporosis influences the late period of fracture healing in a rat model prepared by ovariectomy and low calcium diet.

To elucidate the influence of osteoporosis on the fracture healing, we produced a rat osteoporosis model by ovariectomy and by maintaining a low calcium diet; and monitored the healing process radiographically, histologically, and biomechanically for 12 weeks. Radiologic, histologic and biomechanical findings of the fracture areas 6 weeks after making the fractures were almost identical in both the osteoporosis group and the control group. However, 12 weeks after making the fractures, newly generated bones in the osteoporosis group showed histological osteoporotic changes and their bone mineral density on the fracture site decreased. These findings show that estrogen-deficient and low calcium conditions greatly affect the bone in the later period of the healing process, but do not affect remarkably the early healing period. This is clinically important when we consider fracture treatments for patients with osteoporosis due to menopause.

Animals↗

PubMed1999

Osteoporosis and eating disorders.

Osteoporosis is a common complication of anorexia nervosa. Multiple factors increase risk, including decreased body weight and fat content, elevated cortisol levels, inadequate vitamin D and calcium intake, and amenorrhea and hypoestrogenemia. There is both decreased bone formation and increased bone resorption in the osteoporosis of anorexia nervosa. Treatment includes weight normalization and supplemental calcium and vitamin D. Unlike postmenopausal osteoporosis, estrogen replacement does not prevent or correct the osteoporosis that occurs in anorexia nervosa. Patients with bulimia nervosa or an eating disorder not otherwise specified may also be at risk of osteoporosis, especially if they have had a prior episode of anorexia nervosa.

Adolescent↗

PubMed2006

Vitamin D insufficiency in male osteoporosis.

Osteoporosis is an important public health issue among men, affecting up to 20% of all men in the United States >50 years of age. The social and economic costs of male osteoporosis are profound but can be minimized by a preventive approach, including early identification and treatment of men at risk for this potentially crippling disease. As part of this preventive approach, clinicians should screen susceptible patients for vitamin D deficiency, a commonly occurring, highly correctable risk factor for osteoporosis. Appropriate detection of vitamin D deficiency in men at risk for osteoporosis and adequate correction of this deficiency will significantly reduce morbidity and mortality associated with male osteoporosis.

Calcifediol↗

PubMedDate not supplied

Pharmacotherapeutics for osteoporosis prevention and treatment.

Osteoporosis is a silent disease that affects 10 million Americans; 80% of those affected are women. Although the disease is more common in postmenopausal Caucasian women, all ages and races are at risk. Osteoporosis can be a debilitating disease that can cause pain, fractures, depression, and social withdrawal. Signs of osteoporosis include kyphosis, loss of height, and protrusion of the abdomen. Because symptoms generally do not occur until after the disease has progressed, clinicians should include osteoporosis screening and preventative education as part of the regular gynecologic care. Diagnosis is typically made by a dual energy x-ray absorptiometry (DEXA) scan. Treatment consists of dietary and lifestyle changes, along with pharmacologic intervention. Although hormone therapy has been shown to be effective in preventing osteoporosis, the risks of long-term treatment with HRT are discussed. The following effective treatment options for women who have been diagnosed with the disease are discussed: bisphosphonates, calcitonin, and selective estrogen receptor modulators (SERMs). Because midwives regularly care for women of all ages, they are ideal candidates to provide women with preventative education, screening, counseling, and treatment.

Absorptiometry, Photon↗

PubMed2001

Seeking genetic causes of "osteoporosis:" insights of the Utah paradigm of skeletal physiology.

This article investigates: (1) the criteria used to select cohorts of patients for study when seeking genetic causes of "osteoporosis;" (2) the possibilities, genetic and otherwise, that might cause or help to cause this disorder; and (3) how one should define this disorder and bone health. Patients selected for such a study because current World Health Organization (WHO) absorptiometric criteria diagnosed them with "osteoporosis," or because they had extremity bone fractures, could possibly include people with biologically different disorders, in addition to those with healthy or diseased bones. Seeking a common genetic cause of "osteoporosis" in such inhomogeneous cohorts may be like seeking a common genetic cause of "anemia" in a cohort that contained iron deficiency and pernicious anemias, thalassemia, sickle-cell disease, anemias due to blood loss, malnutrition, malaria, metastatic disease, etc. The Utah paradigm's insights suggest how to select more homogeneous cohorts for such studies. This would require defining bone health in a way that acknowledges the main purpose of load-bearing bones, which the WHO criteria do not do. The present understanding of bone physiology indicates that many biologic mechanisms and features could cause or help to cause an osteopenia or osteoporosis. This study identifies 30 such mechanisms, some osseous and some extraosseous, and even this number seems conservative. Because each such mechanism could depend on any number of genes, when a strong genetic association with some kind of osteopenia or osteoporosis is found it could be difficult to determine which mechanism(s) it perturbed. This article summarizes the evidence and ideas on which these suggestions depend.

Bone Remodeling↗

PubMed2002

Optimal age for preventing osteoporosis after menopause depends on effects of stopping treatment.

The aim of this study was to model the effect of short (3 year) treatments for osteoporosis at different times after menopause on the risk of osteoporotic fracture and to assess the impact of strategies to target high-risk individuals. Treatment efficacy for hip, proximal forearm, shoulder, and spine fracture were computed from the relationship between bone mineral density (BMD) and fracture in women from Sweden. Treatment that increased hip bone mineral density by 6% over untreated women saved 126 vertebral, hip, proximal humerus, and forearm fractures per 1000 women at the age of 50 years, provided that the effects of treatment persisted. Targeting women with osteoporosis at this age would save an additional 50% of fractures. With age, the number of fractures saved decreased moderately. At the age of 70 years, 133 fractures would be saved in women with osteoporosis compared to 198 in women with osteoporosis at the age of 50 years. Where the effect of treatment was assumed to wear off over 20 years after stopping treatment, the efficacy of treatment was reduced at all ages, but most markedly at the age of 50 years. Where all women aged 50 years were treated, the number of fractures saved per 1000 women decreased from 127 to 15 and, in the case of targeting women with osteoporosis, decreased from 198 to 27 per 1000 women. By contrast, with a persisting effect of treatment, the number of fractures saved increased markedly with advancing age. If all women were targeted at the age of 50 years, 15 fractures would be saved, whereas this increased to 55 per 1000 women at the age of 70 years. When treatment effects wore off more rapidly with an offset half-time of 2.5 years only 5 fractures were saved per 1000 women at the age of 50 years. This figure rose to 23 per 1000 at the age of 70 years. We conclude that, although uncertainty exists concerning the offset of effect of treatments, treatments should be optimally given to women without prior fractures in later life.

Age Factors↗

PubMed1999

Osteoporosis in adult patients with celiac disease.

We investigated the bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in adult celiac patients with varying disease states. In this cross-sectional study the data on the severity of celiac disease and BMD were collected from 77 celiac patients (28 newly diagnosed and 49 previously diagnosed celiac patients), and BMD results were compared with those of 157 control subjects matched for age, gender, and menopausal status. The celiac patients had significantly lower BMD than the control subjects at the lumbar spine (-6%) and femoral neck (-5%). The mean BMD did not differ significantly among celiac patients classified by severity of disease. Based on Z scores, 35% of the celiac patients and 17% of the control subjects had low BMDs for age at the lumbar spine (p = 0.005), whereas 31% of celiac patients and 16% of control subjects had Z scores of < or =-1 at the femoral neck (p = 0.01). Altogether, 26% of all celiac patients, but only 5% of control subjects, were classified as having osteoporosis (T score < or =-2.5 SD) at the lumbar spine (p = 0.03), whereas osteoporosis was rare at the femoral neck in both groups (3% vs. 1%, p = 1.00). Prevalence of osteopenia and osteoporosis was highest in newly diagnosed celiac patients and in patients with disease not in remission. A low 25-(OH)D vitamin concentration was a typical biochemical abnormality in our patients (64% of men and 71% of women). The main associated variables of low BMD were age (men), low serum vitamin D level, low body weight, and postmenopausal status (women). The present study suggests that celiac disease constitutes a risk factor for osteoporosis. This finding applies particularly to untreated and poorly treated patients.

Absorptiometry, Photon↗

PubMed2001

Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis.

Aging of the human skeleton is characterized by decreased bone formation and bone mass and these changes are more pronounced in patients with osteoporosis. As osteoblasts and adipocytes share a common precursor cell in the bone marrow, we hypothesized that decreased bone formation observed during aging and in patients with osteoporosis is the result of enhanced adipognesis versus osteoblastogenesis from precursor cells in the bone marrow. Thus, we examined iliac crest bone biopsies obtained from 53 healthy normal individuals (age 30-100) and 26 patients with osteoporosis (age 52-92). Adipose tissue volume fraction (AV), hematopoietic tissue volume fraction (HV) and trabecular bone volume fraction (BV) were quantitated as a percentage of total tissue volume fraction (TV) (calculated as BV + AV + HV) using the point-counting method. We found an age-related increase in AV/TV (r = 0.53, P < 0.001, n = 53) and an age-related decline in BV/TV (r = -0.46, P < 0.001, n = 53) as well as in the HV/TV (r -0.318, P < 0.05, n = 53). There was an age-related inverse correlation between BV/TV and AV/TV (r = -0.58, P < 0.001). No significant correlation between the AV/TV and the body mass index (r = 0.06, n.s., n = 52) was detectable. Compared with age-matched controls, patients with osteoporosis exhibited an increased AV/TV (P < 0.05) and decreased BV/TV (P < 0.05) but no statistically significant difference in HV/TV. Our data support the hypothesis that with aging and in osteoporosis an enhanced adipogenesis is observed in the bone marrow and that these changes are inversely correlated to decreased trabecular bone volume. The cellular and molecular mechanisms mediating these changes remain to be determined.

Adipocytes↗

PubMed2006

Nutritional status, as determined by the Mini-Nutritional Assessment, and osteoporosis: a cross-sectional study of an elderly female population.

OBJECTIVE: To investigate the relationship between osteoporosis and nutritional status as determined by the Mini-Nutritional Assessment (MNA). DESIGN: A cross-sectional study. SETTING: Stockholm, Sweden. SUBJECTS: A total of 351 elderly free-living women (mean age 73+/-2.3 years). METHODS: MNA (range 0-30 points; <17 indicates malnutrition, 17.5-23.5 risk of malnutrition and >or=24 well nourished), measurements of bone mineral density of the left hip and lumbar spine using Hologic QDR 4500, and of the heel using Calscan DEXA-T. RESULTS: The median MNA score was 27 (range 12.5-30). One woman was classified as malnourished and 7.4% were at risk of malnutrition. Osteoporosis of the femoral neck was observed in 22% and a fracture after the age of 50 was reported by 31% of the participants. The following items in the MNA questionnaire exhibited an increased risk of having osteoporosis in the femoral neck and/or total hip: an MNA score of <27 (odds ratio (OR)=2.09; CI=1.14-3.83); a mid-arm circumference of less than 28 cm (OR=2.97; CI=1.29-6.81); and regular use of more than 3 drugs each day (OR=2.12; CI=1.00-4.50). A body weight of more than 70 kg exhibited a decreased risk of having osteoporosis (OR=0.31; CI=0.14-0.70). CONCLUSIONS: In general, the nutritional status was good in this population of free-living elderly women. Nevertheless, half of the women who displayed an MNA score <27 points had a twofold increased risk of having osteoporosis. SPONSORSHIP: Karolinska Institutet, Stockholm County Council.

Absorptiometry, Photon↗

PubMed2002

Corticosteroid-induced osteoporosis in patients with uveitis.

AIMS: To estimate the prevalence of low bone density and osteoporosis in a population of patients with uveitis taking systemic steroid treatment; to clarify the risks of steroid-induced fracture and to suggest a protocol for the prevention and management of bone loss in patients with ophthalmic inflammatory disease. METHODS: Bone densitometry was performed on 129 adult patients with prednisolone-treated uveitis from four centres. Information on uveitis diagnosis, associated risk factors, steroid dosage and treatment duration, prophylaxis and management, was collected. Juveniles, patients with scleritis and those who had used deflazacort, were excluded. RESULTS: Steroid treatment time varied from 13 weeks to 31 years, and the total dosage from 1.29 g to 166.5 g. Twenty-six percent of patients also used one or more immunosuppressives. Forty-eight percent had additional risk factors for bone loss. Bone density was abnormally low in 44.2%, and 15.5% had osteoporosis. Osteoporosis was substantially more common in males (20.6%, all under 60 yrs) than in females (9.8%). Seven symptomatic fractures occurred in patients on treatment. Bone loss correlated with total steroid dose, mean dose, duration of treatment and the presence of pre-existing risk factors. CONCLUSIONS: The prevalence of steroid-induced osteoporosis and fracture is low for patients with uveitis but young males are at risk. Patients at high risk should be identified, and prophylaxis and treatment should be used as required. The guideline of the National Osteoporosis Society is recommended as a management protocol.

Adult↗

PubMed2006

Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem.

Osteoporosis in hemodialysis patients is associated with high morbidity and mortality and, although extensively studied by noninvasive methods, has never been assessed through bone biopsy. The aim of this study was to use histomorphometry to evaluate osteoporosis and identify factors related to its development in hemodialysis patients. We conducted a cross-sectional study involving 98 patients (35 women and 63 men; mean age: 48.4 +/- 13 years) on hemodialysis for 36.9 +/- 24.7 months. Patients were submitted to transiliac bone biopsy with double tetracycline labeling. The bone metabolism factors ionized calcium, phosphorus, bone alkaline phosphatase, deoxypyridinoline, intact parathyroid hormone, and 25(OH) vitamin D were evaluated, as were the bone remodeling cytokines osteoprotegerin (OPG), soluble receptor-activator of NF-kappabeta ligand (sRANKL) and tumor necrosis factor-alpha (TNF)alpha. Osteoporosis was defined as trabecular bone volume (BV/TV) greater than 1 s.d. below normal (men <17.4%; women <14.7%). Forty-five patients (46%) presented osteoporosis, which was correlated with white race. We found BV/TV to correlate with age, OPG/sRANKL ratio, TNFalpha levels, and length of amenorrhea. In multiple regression analysis adjusted for sex and age, length of amenorrhea, white race, and OPG/sRANKL ratio were independent determinants of BV/TV. Histomorphometric analysis demonstrated that osteoporotic patients presented normal eroded surface and low bone formation rate (BFR/BS). Osteoporosis is prevalent in hemodialysis patients. Low BFR/BS could be involved in its development, even when bone resorption is normal. Cytokines may also play a role as may traditional risk factors such as advanced age, hypogonadism, and white race.

Adult↗

PubMed2001

Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis.

Bone mineral density (BMD) and biochemical markers of bone metabolism were analyzed in 67 adults with ALL (n = 27), AML (n = 14), MDS (n = 6) and CML (n = 20) before and after allogeneic stem cell transplantation (SCT). Median age was 36 years (17-56). Twenty-six out of 53 patients (49%) had osteopenia and osteoporosis before SCT, 21/26 had acute leukemias and 5/26 had chronic myeloid leukemia (CML). T-score before SCTwas -1.23 in patients with acute leukemias and 0.62 in CML patients (P = 0.001). After SCT, a significant loss of BMD was observed in all patients. After 6 months, 24 of 36 evaluable patients (67%) had pathologic BMD, 11 of them (30%) had developed osteoporosis. After 12 months, 20 of 32 evaluable patients (62%) had BMD values below normal and nine of them (28%) had osteoporosis. Increased pyridinium excretion was observed in 12/20 patients (60%) with acute leukemias, but only in 3/13 (23%) with CML (P = 0.014). A prolonged vitamin D deficiency for more than 6 months developed early after SCT in all patients. Patients with acute leukemias frequently have osteopenia and osteoporosis before SCT. After SCT, a further loss of BMD occurs independent from the underlying disease. Standard prophylactic measures are not sufficient to prevent loss of bone mass. Studies on prophylactic interventions are needed to prevent severe osteoporosis in long-term survivors of SCT.

Adolescent↗

PubMed1998

Intestinal calcium absorption in men with spinal osteoporosis.

OBJECTIVE: To investigate the role of serum 1,25-dihydroxyvitamin D (1,25D) in the decreased calcium absorption found in men with osteoporosis. DESIGN: Prospective study of patients referred to a university teaching hospital clinic for investigation of possible osteoporosis. PATIENTS: Male patients referred for investigation for osteoporosis, from 1981 to 1995, because of specific risk factors or radiological suspicion of osteoporosis. Men with vertebral compression fractures were compared with those without. MEASUREMENTS: Height and weight, radiocalcium absorption, serum 1,25D and fasting urinary calcium and hydroxyproline excretion. RESULTS: The men with vertebral fractures had higher fasting urinary hydroxyproline excretion (P = 0.003) and lower calcium absorption (P = 0.002) than the men without. Calcium absorption was positively related to 1,25D in both groups but the estimated calcium absorption at zero 1,25D was lower in the osteoporotic than the normal group. 1,25D was lower in the osteoporotic group than in the normal group. However this difference could only explain about half of the difference in calcium absorption between the groups. CONCLUSIONS: Calcium absorption is low in men with osteoporosis. About half of the deficit is due to low serum 1,25-dihydroxy vitamin D levels but there appears, in addition, to be some intestinal resistance to its effect on calcium absorption.

Adult↗

PubMed1999

Vitamin D analogs: from renal bone disease to osteoporosis.

The history of the use of vitamin D metabolites and analogs in clinical medicine began with their use in renal bone disease following the appreciation that the kidney is the major site of the 1 alpha-hydroxylase of vitamin D. In the presence of advanced renal failure, production of calcitriol is impaired and treatment is viewed conceptually as a hormone replacement therapy. Since then, there has been much interest in the rationale for the use of such compounds in osteoporosis. Arguments have been variously forwarded that osteoporosis is in part due to either a defective 1 alpha-hydroxylase occurring at menopause or in later life or to target tissue resistance to calcitriol; some argue that disturbances in vitamin D metabolism are irrelevant to osteoporosis, being either a consequence of aging or a result, not a cause, of osteoporosis itself. This paper reviews these various issues and explores the differences and similarities between the pathogenesis of renal bone disease and osteoporosis.

Animals↗

PubMed2003

Identifying older Chinese immigrants at high risk for osteoporosis.

BACKGROUND: Data about whether Asian Americans are a high-risk or a low-risk group for osteoporosis are limited and inconsistent. Few previous studies have recognized that the heterogeneity of the Asian American population, with respect to both nativity (foreign- vs U.S.-born) and ethnicity, may be related to osteoporosis risk. OBJECTIVE: To assess whether older foreign-born Chinese Americans living in an urban ethnic enclave are at high risk of osteoporosis and to refer participants at high risk for follow-up care. DESIGN: Cross-sectional survey and osteoporosis screening, undertaken as a collaborative project by the Chinese American Service League and researchers at the University of Chicago. SETTING: Chicago's Chinatown. PARTICIPANTS: Four hundred sixty-nine immigrant Chinese American men and women aged 50 and older. MEASUREMENTS AND MAIN RESULTS: Chinese Americans in this urban setting are generally recent immigrants from south China with limited education and resources: mean age at immigration was 54, 56% had primary only or no education, and 57% reported "fair" or "poor" self-rated health. Eighteen percent are uninsured and 55% receive Medicaid. Bone mineral density (BMD) of the calcaneus was estimated using quantitative ultrasound. Immigrant Chinese women in the study had lower average BMD than reference data for white women or U.S.-born Asian Americans. BMD for immigrant Chinese men in the study was similar to white men at ages 50 to 69, and lower at older ages. Low body mass index, low educational attainment and older age at immigration were all associated with lower BMD. CONCLUSIONS: Foreign-born Chinese Americans may be a high-risk group for osteoporosis.

Aged↗

PubMed2002

[Osteoporosis in premenopausal women].

Osteoporosis is a systemic disease of bone, which is characterized by decreased bone mass and changes in the microarchitecture of bone tissue followed by brittleness of bones and increased risk of fractures. Osteoporosis frequently is a disease of postmenopausal women, nevertheless, in rare cases, osteoporosis can also occur in young adults. There are only few studies on the pathophysiology of "premenopausal osteoporosis"; in addition to idiopathic forms, osteoporosis in young women can be caused by glucocorticoid treatment, by eating disorders or can be associated with pregnancy.

Adult↗