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PubMed2004

Validation and comparative evaluation of the osteoporosis self-assessment tool (OST) in a Caucasian population from Belgium.

BACKGROUND: Risk indices have been developed to identify women at risk of low bone mineral density (BMD) who should undergo BMD testing. AIM: To compare the performance of four risk indices in White ambulatory women in Belgium. DESIGN: Epidemiological cross-sectional study. METHODS: Records were analysed for 4035 postmenopausal White women without Paget's disease or advanced osteoarthritis, seen at an out-patient osteoporosis centre between January 1996 and September 1999. Osteoporosis risk index scores were compared to bone density T-scores. The ability of each risk index to identify women with low BMD (T-score < -2.0) or osteoporosis (T < -2.5) was evaluated. RESULTS: Using an Osteoporosis Self-Assessment Tool (OST) score <2 to recommend DXA referral, sensitivity ranged from 85% at the lumbar spine to 97% at the total hip to detect BMD T-scores of <or= -2.5, and specificity ranged from 34% at the total hip to 37% at the femoral neck and lumbar spine. The negative predictive value was high at all skeletal sites (89-99%), demonstrating the usefulness of the OST to identify patients who have normal BMD and should not receive DXA testing. All risk indices performed similarly, although the OST had somewhat better sensitivity and somewhat lower specificity than the other indices at the cut-offs evaluated. Among the 11-12% of women who were classified as highest risk using OST or the Osteoporosis Index of Risk (OSIRIS), 81-85% had low bone mass and 68-74% had osteoporosis. DISCUSSION: The performance of these risk indices among women in Belgium was similar to that reported earlier for other samples in Asian countries, the US, and the Netherlands. The OST and other risk indices are effective and efficient tools to help target high-risk women for DXA testing.

Absorptiometry, Photon↗
PubMed2002

Postmenopausal survivors of breast cancer at risk for osteoporosis: nutritional intake and body size.

Postmenopausal survivors of breast cancer for whom hormone replacement therapy is contraindicated are at risk for development of osteoporosis. The primary purpose of this article is to describe, in a sample of 30 postmenopausal survivors of breast cancer, their calcium and vitamin D intake compared with recommended dietary guidelines for those nutrients for postmenopausal women not taking hormone replacement therapy and the body mass index of these women as nutritional status risk factors for development of osteoporosis. Bone health and presence of osteoporosis were determined by bone mineral density testing of the spine, hip, and forearm. To obtain calcium and vitamin D intake, including supplements, 3-day diet records were completed; height and weight measures were used to calculate body mass index. The sample participants ranged in age from 42 to 65 years; the majority (56%) had been menopausal or off hormone replacement therapy for 5 years or less, and 70% had completed breast cancer treatment for 5 years or less (except tamoxifen). The majority (63%) were of medium body frame size; 30% were of small frame size. The mean body mass index (27.3) and mean weight (160 lbs) indicate that these women, as a group, were over-weight. Although a large percent (63%) were taking calcium supplements, the mean daily intake (diet and supplements) of calcium (1,353 mg) and vitamin D (403 IU) was less than the recommended dietary guidelines for these nutrients in this population. At study entry, 80% of the women were osteopenic (60%) or osteoporotic (20%) and none was receiving treatment/prevention for osteoporosis; only 1 had a previous known osteoporosis diagnosis. This is a special group of women for whom screening and preventive strategies for osteoporosis are imperative.

Adult↗
PubMedDate not supplied

Female adolescents' knowledge of bone health promotion behaviors and osteoporosis risk factors.

PURPOSE: The purpose of this study was to explore female adolescents' knowledge about osteoporosis risk factors and the role of dietary calcium and exercise in the prevention of osteoporosis. METHOD: A descriptive survey design was used in this research. SAMPLE: A convenience sample of 107 adolescent girls in grades 6-10 who attended a public school in southwestern Michigan participated in this study. RESULTS: Of 17 questions related to knowledge of osteoporosis risk factors, only 3 of the factors that are most well known to the public (being a woman, having low intake of dairy products, and a lack of adequate exercise) were correctly identified by a majority of the participants. Knowledge of dietary sources of calcium was primarily limited to dairy products. Participants knew that regular exercise was necessary to prevent osteoporosis, but few could identify the weight-bearing exercises most beneficial for promoting bone health. CONCLUSIONS: Overall, the knowledge of these adolescents, who are in a crucial period of their lives for accruing bone mineral, had limited knowledge of the risk factors for osteoporosis, calcium-rich foods and dietary calcium requirements, and the type of exercise needed to maximize their bone mineral density. Nurses can work with children, adolescents, their families, and other professionals in interventions to prevent osteoporosis in later years.

Adolescent↗
PubMed1998

Morphogenesis of vertebral deformities in involutional osteoporosis. Age-related, three-dimensional trabecular structure.

STUDY DESIGN: The relation between the semiquantitative data of alteration in three-dimensional trabecular structure and deformities of the vertebral body was analyzed to clarify the morphogenesis of vertebral deformities in involutional osteoporosis. OBJECTIVES: To evaluate semiquantitatively the age-related alterations of the three-dimensional structure of trabeculae of the vertebral body and to clarify their relation to vertebral deformities in involutional osteoporosis. SUMMARY OF BACKGROUND DATA: Recent studies have shown that bone fractures and deformities in osteoporosis do not depend only on a reduced amount of bone tissue. There is no previous study on the relation between bone deformity and the alterations of the three-dimensional structure of trabeculae. METHODS: The second lumbar vertebrae were removed at autopsy from 25 patients who had no disease predisposing them to secondary osteoporosis and no severe vertebral deformities. The sections of the vertebral body were immersed in sodium hypochlorite solution to corrode the bone marrow. Atrophy of trabeculae and increased spacing between trabeculae were evaluated semiquantitatively under stereoscopic microscopy. The authors examined the relation between the semiquantitative data found in the autopsy vertebrae and the patterns and frequencies of each deformity of the second lumbar vertebrae in 99 patients with involutional osteoporosis. RESULTS: The most frequent vertebral deformity was wedge-shaped vertebrae with compression of the anterosuperior portion, and the alterations of the trabecular structure of the anterosuperior portion were severe and closely related to aging. Severe trabecular alterations with no relation to aging did not necessarily cause vertebral deformity. CONCLUSIONS: Trabecular abnormality, which is significantly correlated with aging, may be the necessary and sufficient condition for vertebral deformities in involutional osteoporosis.

Aged↗
PubMed2002

Bone densitometry, steroids and osteoporosis.

PURPOSE OF REVIEW: Scans to measure bone mineral density at the spine and hip have an important role in the evaluation of patients at risk of osteoporosis. Oral corticosteroid use is an important risk factor for a fragility fracture and the relative risk is particularly high for vertebral and hip fractures. In Europe and the USA, guidelines have been published for the investigation of patients at risk of corticosteroid-induced osteoporosis, with recommendations on the diagnostic use of bone mineral density scans and the initiation of treatment based on the findings. RECENT FINDINGS: Large trials of bisphosphonates, selective oestrogen receptor modulators and parathyroid hormone have addressed the issue of fracture prevention in women with postmenopausal osteoporosis and there is a growing consensus that the World Health Organization definition of osteoporosis of a -score=-2.5 is an appropriate threshold for preventive treatment in these patients. For most agents separate studies have been conducted of their use for the prevention and treatment of corticosteroid-induced osteoporosis. SUMMARY: There is increased awareness of the importance of preventive treatment for osteoporosis in patients taking high doses of oral corticosteroids (daily dose of 7.5 mg prednisolone or greater). In view of evidence that corticosteroid use is an independent risk factor for fracture over and above bone mineral density, guidelines for intervention set a higher threshold than the World Health Organization figure ( -score=-1.5 rather than -2.5) for intervention with bone sparing treatment in these patients.

Aged↗
PubMedDate not supplied

A familial risk profile for osteoporosis.

PURPOSE: To describe genetic epidemiologic aspects of osteoporosis. METHODS: 69 patients with osteoporosis were interviewed regarding personal and family histories of osteoporosis and related fractures. Family history information was obtained on 421 first degree and 748 second degree relatives. RESULTS: 45% of cases reported a family history of osteoporosis. Familial cases were characterized neither by an earlier age of diagnosis nor by a greater degree of phenotypic severity. Empiric risks for osteoporosis were highest for mothers, 33%, and were 19% for sisters. CONCLUSION: These results provide an initial genetic epidemiologic profile for osteoporosis and information useful for genetic counseling.

Adult↗
PubMed2003

HIV infection--a risk factor for osteoporosis.

Osteopenia and osteoporosis have recently been described as complications of antiretroviral therapy in HIV-infected patients. The advent of highly active antiretroviral therapy in conjunction with improved standard antiviral and antibiotic regimens has dramatically changed the clinical course of HIV infection, resulting in prolonged survival. The pathogenesis and role of each individual medication are poorly understood. Avascular necrosis has also been described in AIDS patients receiving or not receiving antiretroviral therapy. This article is a clinically focused review of the literature on osteopenia, osteoporosis, and mineral metabolism related to HIV infection. In patients with HIV infection, the risks of osteopenia and osteoporosis are not very clear. The suggested risk factors for the development of osteopenia are use of protease inhibitors, longer duration of HIV infection, high viral load, high lactate levels, low bicarbonate levels, raised alkaline phosphatase level, and lower body weight before antiretroviral therapy. There have also been a few case reports of pathologic fractures in AIDS patients with antiretroviral therapy-induced osteopenia and osteoporosis. The underlying mechanism triggering bone loss in HIV-infected patients is unknown. The proinflammatory cytokines tumor necrosis factor and interleukin-6 have been found to be constitutionally produced in increased amounts in HIV-positive individuals, and they may have a role in osteoclast activation and resorption. Serum markers of bone formation are decreased and resorption is increased in patients with advanced clinical disease. Hypocalcemia, hypercalcemia, and abnormalities of the parathyroid hormone axis have been described in HIV infection. Histomorphometric analyses have shown altered bone remodeling in HIV-infected patients when compared with controls. Patients with known risk factors for osteoporosis-advancing age, low body weight, and prolonged duration of HIV infection-and those receiving protease inhibitor treatment should be considered for dual x-ray absorptiometry imaging. If bone mineral density is osteopenic or osteoporotic, then the patient should also be screened for other known medical causes of osteoporosis and consider treatment with a bisphosphonate or, if hypogonadal, testosterone replacement under close monitoring.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Genetic determinants of osteoporosis.

PURPOSE OF REVIEW: Osteoporosis is a common disease with a strong genetic component characterised by reduced bone mass and an increased risk of fragility fractures. Several advances have been made over recent years in understanding the genetic basis of susceptibility to osteoporosis. This paper will review recent developments in this area. RECENT FINDINGS: Twin studies have shown that genetic factors contribute to osteoporosis by influencing bone mineral density and other determinants of fracture risk such as ultrasound properties of bone, skeletal geometry, and bone turnover. In the normal population, many different genes contribute to the regulation of these phenotypes by interacting with environmental factors such as diet and exercise. Whereas the effect size of individual genes is small, meta-analysis has been successfully used in many cases to define the role of individual polymorphisms in predisposing to osteoporosis. Linkage studies in humans and experimental animals have identified several quantitative trait loci that regulate osteoporosis-related phenotypes, and many genes that cause monogenic bone diseases have been identified by use of this approach. It has been found that subtle polymorphisms in some of these genes also contribute to regulation of bone mass in the normal population. SUMMARY: Research has recently begun to clarify the genes and genetic variants that predispose to osteoporosis and regulation of bone mass. Clinical applications of this research include the identification of genetic markers for assessment of fracture risk and the identification of novel molecular targets for the design of drugs that can be used to treat bone disease.

Animals↗
PubMedDate not supplied

Barriers to providing osteoporosis care in skilled nursing facilities: perceptions of medical directors and directors of nursing.

OBJECTIVES: The objectives of this study were to identify the barriers to osteoporosis clinical practice guideline use perceived by Medical Directors (MED DIR) and Directors of Nursing (DON) in skilled nursing facilities; and to describe differences in the perceptions of MED DIRs and DONs. DESIGN: The authors conducted a cross-sectional national survey. PARTICIPANTS: This study consisted of a random national sample of MED DIRs (n=1300) and DONs (n=1300) belonging to the American Medical Directors Association or the National Association of Directors of Nursing Administration in Long-term Care. MEASUREMENTS: A 24-item survey using a five-point Likert scale was developed. The survey measured agreement to questions in four domains (provider factors, guideline characteristics, patient factors, environmental factors) and 10 content areas (problem acknowledgment, patient/family concern, patient/family compliance, testing availability, safety, reimbursement, regulatory oversight, staff knowledge/time/ability, belief in guidelines, and malpractice liability). Response distributions to each item were plotted and differences between MED DIRs and DONs were tested. RESULTS: Survey response rates were 40% for MED DIRs and 48% for DONs. Respondents strongly agreed that fractures are a problem in their facilities and that osteoporosis guidelines are useful and cost-beneficial (mean responses > or = 4.0). A large proportion of respondents (at least 40% of the sample) identified multiple patient comorbidities, reimbursement issues, length of stay, and regulatory oversight as barriers to providing osteoporosis care. Respondents did not believe that patient and family acceptance, testing availability, staff time, staff self-efficacy, or concerns about bisphosphonate safety were barriers to osteoporosis care. DONs were more likely than MED DIRs to believe that patients and families are concerned about fractures, whereas MED DIRs were more likely to endorse length of stay, staffing issues, and regulatory oversight as influencing treatment decisions. Years of practice and facility size, but not formal geriatrics training, significantly influenced responses. CONCLUSION: Perceived barriers to implementing osteoporosis guidelines differ between facilities and between MED DIRs and DONs. Identification of these barriers could facilitate quality improvement initiatives and improve the quality of osteoporosis care.

Attitude of Health Personnel↗
PubMed2004

The diagnosis and treatment of osteoporosis in men on androgen deprivation therapy for advanced carcinoma of the prostate.

PURPOSE: Androgen deprivation therapy (ADT) for advanced prostate cancer increases the risk of osteoporosis. Thus, the practicing urologist should be aware of the appropriate assessment and management. In this article we review the tests designed to diagnose osteoporosis as well as treatment options. We also review methods to monitor the response to therapy and make recommendations for management. MATERIALS AND METHODS: We performed a MEDLINE (1966 to 2004) search for the terms male, osteoporosis, bone mineral density, prostate cancer, androgen deprivation therapy, bisphosphonates, estrogen and the combinations thereof. We then constructed a management algorithm based on the best evidence available. RESULTS: Dual energy x-ray absorptiometry of the hip is the gold standard test for osteoporosis. Biochemical markers of bone turnover are not suitable for diagnosis but they have been shown to be useful for monitoring the response to treatment. Smoking cessation, weight bearing exercise, and vitamin D and calcium have been shown to help improve bone mineral density (BMD). Bisphosphonates have been demonstrated to increase BMD and decrease fracture risk in men with osteoporosis. Estrogens have also recently been shown to decrease bone turnover and increase BMD in men on ADT. CONCLUSIONS: Hip dual energy x-ray absorptiometry should be performed in all men who are anticipated to be on long-term ADT. In addition, all men on ADT should receive vitamin D and calcium supplementation, and perform regular weight bearing exercise. The value of smoking cessation cannot be overstated. In men who have osteopenia or osteoporosis bisphosphonate therapy should be initiated. Estrogen therapy has shown promise but specific recommendations cannot be made at this time.

Algorithms↗
PubMed2006

Osteoporosis in children with severe congenital neutropenia: bone mineral density and treatment with bisphosphonates.

A high incidence of decreased bone mineral density (BMD) has been described in patients with severe congenital neutropenia (SCN). The objectives of the study are to describe changes in BMD in children with SCN treated with granulocyte colony-stimulating factor and evaluate the response to treatment with bisphosphonates in those who had osteoporosis. A prospective open-label study was performed evaluating BMD and metabolism in 9 Chilean patients with SCN, administrating bisphosphonates in those with osteoporosis. Follow-up ranged between 7 months and 3.5 years. Six out of 9 patients had reduced BMD on initial assessment: 3 had osteoporosis (z score <-2) and 3 had osteopenia (z score <-1). Four children presented vertebral fractures. Two presented osteopenia on follow-up without clinical symptoms. Five patients were treated with bisphosphonates, increasing their BMD z score (mean increase 1.2, range 0.27 to 2.62). z Score of hydroxyproline/creatinine ratios, which was elevated in 4 patients with osteoporosis, decreased during treatment (mean decrease 2.18, range 1.56 to 2.53). Four patients remodeled and reexpanded fractured vertebrae during treatment. No side effects of bisphosphonates were seen on follow-up. Osteoporosis is an important comorbidity in SCN patients probably due to increased bone resorption. Bisphosphonates seem to be an effective treatment for osteoporosis in these patients.

Bone Density↗
PubMed2003

Racial disparities in osteoporosis prevention in a managed care population.

BACKGROUND: Osteoporosis in black women may result in increased disability, longer hospital stays, and higher mortality compared with white women. However, it is unknown whether osteoporosis treatment or bone mineral density (BMD) measurement is different in these women, particularly in those at highest risk. METHODS: To examine differences and determinants of osteoporosis preventive interventions among white and black women in a large regional health maintenance organization, women 50 years of age and older were surveyed (n = 8,909) to determine their receipt of BMD testing and medical therapies for osteoporosis prevention. RESULTS: After adjusting for potential confounders, black women had two- to threefold lower odds of BMD test or osteoporosis prescription treatment. Even among women with a previous fracture, blacks still had a significantly lower likelihood of both BMD testing and prescription therapy. CONCLUSION: Compared with whites, black women reported significantly less BMD testing and prescription and nonprescription osteoporosis therapy. This disparity was not fully explained by other demographic or risk factor differences.

Black or African American↗
PubMed2006

Primary care house staff attitudes toward osteoporosis management.

OBJECTIVE: This study assessed possible institutional and patient-related factors influencing the delivery of postmenopausal osteoporosis (PMO) care and the diagnostic priority placed on addressing PMO, relative to other common medical conditions, by primary care house staff at our institution. METHODS: A questionnaire was designed and distributed to eligible house staff at our institution. RESULTS: Approximately 50% (n = 52) of the house staff participated. The supervising clinic attending, patients' lack of insurance, accessibility to medical care, comorbid conditions, and university formulary were reported to influence decisions regarding osteoporosis care. Osteoporosis was ranked 6th of 7 medical issues (hypertension, coronary artery disease, diabetes, hypercholesterolemia, adult immunizations, osteoporosis, thyroid disease) to address during a comprehensive medical visit. CONCLUSIONS: Our institution's primary care house staff reported multiple influences on decision making regarding osteoporosis care, and an overall low priority to address this issue. Based on PMO's associated morbidity and mortality, primary care training programs are challenged to put resources toward optimizing house staff delivery of osteoporosis care.

Attitude of Health Personnel↗
PubMed1993

Pregnancy associated osteoporosis.

OBJECTIVE: Previous literature reports have suggested that osteoporosis associated with pregnancy is a rare event. We have examined the prevalence of this condition and compiled data on the largest group of such patients in the literature. PATIENTS AND DESIGN: With the help of the National Osteoporosis Society 35 women with pregnancy associated osteoporosis were identified. These women were matched with a control group from our already established computer data bank for age, weight, height and calcium status. Detailed questionnaires were sent to the osteoporotic sufferers enquiring about their present condition, past medical and drug history, and their menstrual, lactational and obstetric histories. They were also asked to complete a detailed dietary history to establish their calcium status. A questionnaire was also completed by the parents of these women and the parents of the control group, asking specifically about fracture history. RESULTS: Twenty-nine women had idiopathic osteoporosis associated with pregnancy, while in six, the condition may have resulted from drug therapy or associated diseases. Pain occurring late in the first full term pregnancy was the most common presentation. The natural history was for the condition to improve with time. There was a significantly higher prevalence of adult related fractures (P < 0.02) occurring at an earlier age in the mothers of these women compared to a control population. CONCLUSION: We have identified 35 women who have developed osteoporosis during or shortly after pregnancy and in only six of them could a recognized underlying cause be suggested. These findings would suggest that idiopathic osteoporosis associated with pregnancy may be more common than the current literature suggests. The higher prevalence of fractures in the mothers of our population compared to controls raises the question of a possible associated genetic factor in the aetiology of this condition.

Adult↗
PubMed2004

A preventative health education programme for osteoporosis.

BACKGROUND: Osteoporosis is a preventable disease that is usually not managed until the disease becomes evident, although it places huge economic and social burdens on societies worldwide. It is predicted that this burden will grow if left unchecked. Despite this, evidence suggests that osteoporosis prevention activity is given a low priority, and services often only provide biomedically-based programmes, in which resources are predominantly allocated to screening and pharmacological treatments. Referral to these services mostly occurs when a client is already known to have osteoporosis or to be at risk, rather than as an early preventative intervention. AIM: This paper reports an action research project with one hospital osteoporosis service. The aim of the project was to assess the current service, identify areas where change was needed, and evaluate the implementation of such changes. METHOD: Participatory action research was used, with group meetings and reflective journals to collect data for analysis. The process involved assessment of a preventative osteoporosis service, and determination of clinical issues and problems, and it aided decisions on an appropriate course of organizational reform and evaluated any change processes as they occurred. It also encouraged participants to reflect on and evaluate their experiences of using a participatory framework. CONCLUSION: A change programme was implemented that focused on preventative health education activity in a range of clinical settings. Over the two and a half years of the project, the osteoporosis service expanded its programme to include a wide range of preventative activities, running alongside other organizational reforms.

Health Promotion↗
PubMed2004

Diagnostic performance of quantitative ultrasound calcaneus measurement in case finding for osteoporosis in Thai postmenopausal women.

AIM: Dual-energy X-ray absorptiometry (DXA) is currently considered the gold standard for the diagnosis of osteoporosis. Quantitative ultrasound (QUS) can be an alternative method that is less expensive, portable, and can be used at a primary care level to indicate osteoporosis in women. The present study aimed to assess the diagnostic performance of QUS calcaneus measurement in a case finding for osteoporosis in Thai postmenopausal women using DXA as a gold standard. METHODS: Three hundred postmenopausal women, who had not menstruated normally for at least 1 year, were included in the study. To determine the accuracy and reliability of QUS of the calcaneus, calcaneus bone density measurement was carried out using the QUS and left femoral neck bone density was measured using DXA. Bone mass density (BMD) was interpreted as osteoporotic or normal using WHO criteria for determining the performance of QUS. Optimal cut-off values were determined using a receiver operating characteristic (ROC) curve for diagnosing the osteoporosis cases. RESULTS: The number of osteoporosis cases in this study was 107 (35.67%). The sensitivity, specificity, positive and negative predictive values were 39.25%, 91.71%, 72.41%, 73.14%, respectively, when using the T-score of the WHO criteria as a reference. The positive and negative likelihood ratios were 4.73 and 0.66. When using the ROC curve to determine the optimal cut-off values, using the stiffness index of the QUS and categorizing age (<65 years and >or=65 years) before conducting the test, sensitivity and specificity were 77.6% and 59.6%, respectively. CONCLUSIONS: Bone mass density measurement for predicting osteoporosis using QUS had a very low sensitivity and was not good enough to replace the standard tool (DXA).

Absorptiometry, Photon↗
PubMed1999

Prevention and treatment of osteoporosis in patients with inflammatory bowel disease.

Osteopenia or osteoporosis is common in patients with inflammatory bowel disease. The use of corticosteroids contributes to the decline in bone loss; however, osteoporosis may develop in patients with inflammatory bowel disease independent of corticosteroid use. Risk factors for the development of low bone mass in patients with inflammatory bowel disease include the general risk factors for osteoporosis as well as additional factors such as the presence of chronic inflammation, use of corticosteroids and other pharmaceuticals, and nutritional deficiencies as the result of small bowel disease or small bowel resections. Despite the high prevalence, few patients are entered into prophylactic regimens to prevent corticosteroid-induced bone loss. The American College of Rheumatology has recently published recommendations for the prevention and treatment of corticosteroid-induced osteoporosis. In this article, we highlight the special risks for osteoporosis in patients with IBD and adapt the recommendations for prevention and treatment of osteoporosis to this clinical setting.

Anti-Inflammatory Agents↗
PubMed2004

Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis.

The ideal treatment of osteoporosis should preferably prevent fractures through normalization of bone mass and bone micro-architecture. Biosynthetic human parathyroid hormone 1-34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2-3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 microg/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged.

Amino Acid Sequence↗