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The Lancet. Diabetes & Endocrinology Apr 2022Osteoporosis in men is a common but often overlooked disorder by clinicians. The criterion for osteoporosis diagnosis in men is similar to that in women-namely, a bone... (Review)
Review
Osteoporosis in men is a common but often overlooked disorder by clinicians. The criterion for osteoporosis diagnosis in men is similar to that in women-namely, a bone mineral density (BMD) that is 2·5 standard deviations or more below the mean for the young adult population (aged 20-29 years; T-score -2·5 or lower), measured at the hip or lumbar spine. Sex steroids are important for bone health in men and, as in women, oestrogens have a key role. Most men generally have bigger and stronger bones than women and typically have less bone loss during their lifetime. Men typically fracture less often than women, although they have a higher mortality rate after a fracture. Secondary osteoporosis is more common in men than in women. Lifestyle changes, adequate calcium, vitamin D intake, and exercise programmes are recommended for the management of osteoporosis in men. Bisphosphonates, denosumab, and teriparatide have been shown to increase BMD and are used for pharmacological treatment. In this Review, we report an updated overview of osteoporosis in men, describe new treatments and concepts, and discuss persistent controversies in the area.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Female; Humans; Male; Osteoporosis; Teriparatide
PubMed: 35247315
DOI: 10.1016/S2213-8587(22)00012-2 -
Endocrinology and Metabolism (Seoul,... Jun 2021Osteoporosis is an incurable chronic condition, like heart disease, diabetes, or hypertension. A large gap currently exists in the primary prevention of fractures, and...
Osteoporosis is an incurable chronic condition, like heart disease, diabetes, or hypertension. A large gap currently exists in the primary prevention of fractures, and studies show that an estimated 80% to 90% of adults do not receive appropriate osteoporosis management even in the secondary prevention setting. Case finding strategies have been developed and effective pharmacological interventions are available. This publication addresses how best to use the pharmacological options available for postmenopausal osteoporosis to provide lifelong fracture protection in patients at high and very high risk of fracture. The benefit of osteoporosis therapies far outweighs the rare risks.
Topics: Bone Density Conservation Agents; Diphosphonates; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 34154042
DOI: 10.3803/EnM.2021.301 -
Current Opinion in Pediatrics Dec 2019The purpose of this review is to outline the current understanding of the molecular mechanisms and natural history of osteogenesis imperfecta, and to describe the... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to outline the current understanding of the molecular mechanisms and natural history of osteogenesis imperfecta, and to describe the development of new treatments for this disorder.
RECENT FINDINGS
The introduction of next-generation sequencing technology has led to better understanding of the genetic cause of osteogenesis imperfecta and enabled cost-effective and timely diagnosis via expanded gene panels and exome or genome sequencing. Clinically, despite genetic heterogeneity, different forms of osteogenesis imperfecta share similar features that include connective tissue and systemic manifestations in addition to bone fragility. Thus, the goals of treatment in osteogenesis imperfecta extend beyond decreasing the risk of fracture, to include the maximization of growth and mobility, and the management of extraskeletal complications. The standard of care in pediatric patients is bisphosphonates therapy. Ongoing preclinical studies in osteogenesis imperfecta mouse models and clinical studies in individuals with osteogenesis imperfecta have been instrumental in the development of new and targeted therapeutic approaches, such as sclerostin inhibition and transforming growth factor-β inhibition.
SUMMARY
Osteogenesis imperfecta is a skeletal dysplasia characterized by bone fragility and extraskeletal manifestations. Better understanding of the mechanisms of osteogenesis imperfecta will enable the development of much needed targeted therapies to improve the outcome in affected individuals.
Topics: Adaptor Proteins, Signal Transducing; Animals; Child; Diphosphonates; Humans; Mice; Molecular Targeted Therapy; Osteogenesis Imperfecta
PubMed: 31693577
DOI: 10.1097/MOP.0000000000000813 -
International Journal of Implant... May 2021Medication-related osteonecrosis of the jaw (MRONJ), which was first reported as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in bisphosphonate users, is a... (Review)
Review
BACKGROUND
Medication-related osteonecrosis of the jaw (MRONJ), which was first reported as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in bisphosphonate users, is a rare but severe soft and hard tissue disease induced by several types of medications. There has been a deluge of information about MRONJ, such as epidemiology, risk factors, clinical recommendations for dental treatment to prevent it, and treatment strategies in medication-prescribed users. The aim of this study was to comprehensively review recent articles and provide the current scientific information about MRONJ, especially clinical considerations or recommendations for dental treatment to prevent its occurrence.
MATERIALS AND METHODS
The current literature review was mainly based on 14 systematic reviews with or without meta-analysis, 4 position papers, 1 consensus statement, 1 clinical guideline, and 2 clinical reviews regarding MRONJ after a PubMed database and manual searches according to inclusion and exclusion criteria. Moreover, 53 articles were selected by manual search in regard to all references from selected articles and other articles identified on the PubMed search, irrespective of publication date, and inclusion and exclusion criteria.
RESULTS
The incidence and prevalence of MRONJ are relatively low, although they are clearly higher in cancer patients receiving high-dose antiresorptive agents or angiogenesis inhibitors rather than osteoporosis patients receiving oral bisphosphonates or denosumab. There are many types of local, systemic, and other risk factors for the development of MRONJ. Clinical recommendations are provided for each clinical situation of patients to prevent MRONJ. There are also treatment strategies for MRONJ in each stage.
CONCLUSIONS
General dentists should perform appropriate dental treatment to prevent MRONJ in the patients prior to or when receiving medications that could induce MRONJ. Moreover, there are treatment strategies for MRONJ in each stage that oral surgeons could follow. Adequate and updated clinical information regarding MRONJ based on scientific data is required whenever possible.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Denosumab; Diphosphonates; Humans; Osteoporosis
PubMed: 33987769
DOI: 10.1186/s40729-021-00323-0 -
Archives of Endocrinology and Metabolism Nov 2022It is now well recognized that over the lifetime of a patient with osteoporosis, more than one medication will be needed to treat the disease and to decrease fracture... (Review)
Review
It is now well recognized that over the lifetime of a patient with osteoporosis, more than one medication will be needed to treat the disease and to decrease fracture risk. Though current gaps in osteoporosis therapy can be potentially mitigated with sequential and combination regimens, how to move seamlessly amongst the multiple treatments currently available for osteoporosis for sustained efficacy is still unclear. Data from recent studies show that an anabolic agent such as teriparatide or romosozumab followed by an antiresorptive affords maximal gain in BMD and possibly better and earlier fracture risk reduction compared to a regimen which follows the opposite sequence. Sequentially moving to a bisphosphonate such as alendronate from an anabolic agent such as abaloparatide has also been shown to preserve the fracture reduction benefits seen with the latter. This sequence of an anabolic agent followed by an antiresorptive should especially be considered in the high-risk patient with imminent fracture risk to rapidly reduce the risk of subsequent fractures. The data surrounding optimum timing of initiation of bisphosphonate therapy following denosumab discontinuation is still unclear. Though data suggests that combining a bisphosphonate with teriparatide does not provide substantial BMD gains compared to monotherapy, the concomitant administration of denosumab with teriparatide has been shown to significantly increase areal BMD as well as to increase volumetric BMD and estimated bone strength. This narrative review explores the available evidence regarding the various sequential and combination therapy approaches and the potential role they could play in better managing osteoporosis.
Topics: Humans; Female; Teriparatide; Denosumab; Bone Density Conservation Agents; Bone Density; Osteoporosis; Diphosphonates; Fractures, Bone; Osteoporosis, Postmenopausal
PubMed: 36382762
DOI: 10.20945/2359-3997000000564 -
Women's Health (London, England) 2023Osteoporosis is a systemic skeletal disease that is a cause of morbidity and mortality. It can affect all ages but most frequently postmenopausal women. It is a silent... (Review)
Review
Osteoporosis is a systemic skeletal disease that is a cause of morbidity and mortality. It can affect all ages but most frequently postmenopausal women. It is a silent condition, however, osteoporotic fractures can lead to significant pain and disability. In this review article, we aim to review the clinical approach to the management of postmenopausal osteoporosis. We include risk assessment, investigations, and the various pharmacological and non-pharmacological options used in the treatment of osteoporosis. We have discussed the pharmacological options individually including their mechanism of action, safety profile, effects on bone mineral density and fracture risks, and duration of use. Potential new treatments are also discussed. The importance of sequence in the use of osteoporotic medicine is also highlighted in the article. An understanding of the different treatment options will hopefully help in the management of this very common and debilitating condition.
Topics: Female; Humans; Bone Density Conservation Agents; Teriparatide; Osteoporosis; Osteoporotic Fractures; Osteoporosis, Postmenopausal; Bone Density; Aging; Diphosphonates
PubMed: 37218715
DOI: 10.1177/17455057231176655 -
European Review For Medical and... May 2021Osteoporosis is a metabolic disease of the skeletal system which currently affects over 200 million patients worldwide. The WHO criteria define osteoporosis as low bone... (Review)
Review
Osteoporosis is a metabolic disease of the skeletal system which currently affects over 200 million patients worldwide. The WHO criteria define osteoporosis as low bone mineral density, with a T-score ≤ -2.5 found in the spine, the neck of the femur, or during a full hip examination. Osteoporosis considerably reduces a patient's quality of life. QoL should be carefully evaluated before fractures occur to enable the development of an appropriate treatment plan. The progression of osteoporosis may be significantly inhibited by following a proper diet, leading a healthy lifestyle, taking dietary supplements, and receiving appropriate treatment. Education and the prevention of the disease play a major role. Potentially modifiable risk factors for osteoporosis are vitamin D deficiency, smoking, alcohol consumption, low calcium intake, low or excessive phosphorus intake, protein deficiency or a high-protein diet, excessive consumption of coffee, a sedentary lifestyle or lack of mobility, and insufficient exposure to the sun. Pharmaceutical treatment for osteoporosis involves bisphosphonates, calcium and vitamin D3, denosumab, teriparatide, raloxifene, and strontium ranelate. Data indicates that 30%-50% of patients do not take their medication correctly. Other methods of treatment include exercise, kinesitherapy, treatment at a health resort, physical therapy, and diet.
Topics: Cholecalciferol; Denosumab; Dietary Supplements; Diphosphonates; Exercise; Humans; Kinesiology, Applied; Osteoporosis; Raloxifene Hydrochloride; Risk Factors; Teriparatide; Thiophenes
PubMed: 34002830
DOI: 10.26355/eurrev_202105_25838 -
Bone Dec 2021Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). pARs, including nitrogen-containing bisphosphonates (N-BPs; e.g., zoledronic acid, alendronate) and anti-RANKL antibodies (e.g., denosumab), are used to manage bone metastases in patients with cancer or to prevent fragility fractures in patients with osteoporosis. Though significant advances have been made in understanding MRONJ, its pathophysiology is still not fully elucidated. Multiple species have been used in preclinical MRONJ research, including the rat, mouse, rice rat, rabbit, dog, sheep, and pig. Animal research has contributed immensely to advancing the MRONJ field, particularly, but not limited to, in developing models and investigating risk factors that were first observed in humans. MRONJ models have been developed using clinically relevant doses of systemic risk factors, like N-BPs, anti-RANKL antibodies, or AgIs. Specific local oral risk factors first noted in humans, including tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection, etc.), were then added. Research in rodents, particularly the rat, and, to some extent, the mouse, across multiple laboratories, has contributed to establishing multiple relevant and complementary preclinical models. Models in larger species produced accurate clinical and histopathologic outcomes suggesting a potential role for confirming specific crucial findings from rodent research. We view the current state of animal models for MRONJ as good. The rodent models are now reliable enough to produce large numbers of MRONJ cases that could be applied in experiments testing treatment modalities. The course of MRONJ, including stage 0 MRONJ, is characterized well enough that basic studies of the molecular or enzyme-level findings in different MRONJ stages are possible. This review provides a current overview of the existing models of MRONJ, their more significant features and findings, and important instances of their application in preclinical research.
Topics: Animals; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Diphosphonates; Disease Models, Animal; Dogs; Humans; Mice; Rabbits; Rats; Sheep; Swine
PubMed: 34520898
DOI: 10.1016/j.bone.2021.116184 -
Endocrinology and Metabolism (Seoul,... Oct 2022Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries,...
Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.
Topics: Humans; Osteitis Deformans; Diphosphonates; Pamidronate; Bone and Bones; Bone Resorption
PubMed: 36327984
DOI: 10.3803/EnM.2022.1575 -
The New England Journal of Medicine Aug 2020Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased...
BACKGROUND
Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors.
METHODS
We studied women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated. Multivariable Cox models were used. The risk-benefit profile was modeled for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented.
RESULTS
Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with longer duration of bisphosphonate use: the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval [CI], 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. Other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use. Bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture. Decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians. After 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians.
CONCLUSIONS
The risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation. Asians had a higher risk than Whites. The absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.).
Topics: Aged; Aged, 80 and over; Asian; Bone Density Conservation Agents; Diphosphonates; Female; Femoral Fractures; Hip Fractures; Humans; Incidence; Middle Aged; Multivariate Analysis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; White People
PubMed: 32813950
DOI: 10.1056/NEJMoa1916525