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1.
Osteoporos Int ; 35(1): 1-10, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37982855

RESUMO

Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present.


Assuntos
Hipofosfatasia , Adulto , Criança , Humanos , Adolescente , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Fosfatase Alcalina/genética , Europa (Continente) , Prevalência , Mutação
2.
J Clin Densitom ; 26(4): 101432, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37944445

RESUMO

The Santa Fe Bone Symposium (SFBS) held its 23rd annual event on August 5-6, 2023, in Santa Fe, New Mexico, USA. Attendees participated in-person and remotely, representing many states and countries. The program included plenary presentations, panel discussions, satellite symposia, a Project ECHO workshop, and a session on healthcare policy and reimbursement for fracture liaison programs. A broad range of topics were addressed, including transitions of osteoporosis treatments over a lifetime; controversies in vitamin D; update on Official Positions of the International Society for Clinical Densitometry; spine surgery and bone health; clinical applications of bone turnover markers; basic bone biology for clinicians; premenopausal-, pregnancy-, and lactation-associated osteoporosis; cancer treatment induced bone loss in patients with breast cancer and prostate cancer; genetic testing for skeletal diseases; and an update on nutrition and bone health. There were also sessions on rare bone diseases, including managing patients with hypophosphatasia; treatment of X-linked hypophosphatemia; and assessment and treatment of patients with hypoparathyroidism. There were oral presentations of abstracts by endocrinology fellows selected from those who participated in the Santa Fe Fellows Workshop on Metabolic Bone Diseases, held the 2 days prior to the SFBS. These proceedings of the 2023 SFBS present the clinical highlights and insights generated from many formal and informal discussions in Santa Fe.


Assuntos
Doenças Ósseas Metabólicas , Fraturas Ósseas , Osteoporose , Masculino , Feminino , Humanos , Absorciometria de Fóton , Osteoporose/tratamento farmacológico , Fraturas Ósseas/terapia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/terapia , Densidade Óssea
3.
J Clin Densitom ; 25(4): 649-667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36280582

RESUMO

The 22nd Annual Santa Fe Bone Symposium (SFBS) was a hybrid meeting held August 5-6, 2022, with in-person and virtual attendees. Altogether, over 400 individuals registered, a majority of whom attended in-person, representing many states in the USA plus 7 other countries. The SFBS included 10 plenary presentations, 2 faculty panel discussions, satellite symposia, Bone Health & Osteoporosis Foundation Fracture Liaison Service Boot Camp, and a Project ECHO workshop, with lively interactive discussions for all events. Topics of interest included fracture prevention at different stages of life; how to treat and when to change therapy; skeletal health in cancer patients; advanced imaging to assess bone strength; the state of healthcare in the USA; osteosarcopenia; vitamin D update; perioperative bone health care; new guidelines for managing primary hyperparathyroidism; new concepts on bone modeling and remodeling; and an overview on the care of rare bone diseases, including hypophosphatasia, X-linked hypophosphatemia, tumor induced osteomalacia, osteogenesis imperfecta, fibrodysplasia ossificans progressiva, and osteopetrosis. The SFBS was preceded by the Santa Fe Fellows Workshop on Osteoporosis and Metabolic Bone Diseases, a collaboration of the Endocrine Fellows Foundation and the Osteoporosis Foundation of New Mexico. From the Workshop, 4 participating fellows were selected to give oral presentations at the bone symposium. These proceedings represent the clinical highlights of 2022 SFBS presentations and the discussions that followed, all with the aim of optimizing skeletal health and minimizing the consequences of fragile bones.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Fraturas por Osteoporose , Humanos , Absorciometria de Fóton , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/terapia , Fraturas por Osteoporose/prevenção & controle
4.
J Bone Miner Res ; 37(12): 2435-2442, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36190391

RESUMO

Abaloparatide significantly increased bone mineral density (BMD) in women with postmenopausal osteoporosis and decreased risk of vertebral, nonvertebral, and clinical fractures compared with placebo. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study evaluated the efficacy and safety of abaloparatide compared with placebo in men. Eligible men aged 40 to 85 years with osteoporosis were randomized 2:1 to daily subcutaneous injections of abaloparatide 80 µg or placebo for 12 months. The primary endpoint was change from baseline in lumbar spine BMD. Key secondary endpoints included BMD change from baseline at the total hip and femoral neck. A total of 228 men were randomized (abaloparatide, n = 149; placebo, n = 79). Baseline characteristics were similar across treatment groups (mean age, 68.3 years; mean lumbar spine BMD T-score, -2.1). At 12 months, BMD gains were greater with abaloparatide compared with placebo at the lumbar spine (least squares mean percentage change [standard error]: 8.48 [0.54] versus 1.17 [0.72]), total hip (2.14 [0.27] versus 0.01 [0.35]), and femoral neck (2.98 [0.34] versus 0.15 [0.45]) (all p < 0.0001). The most common (≥5%) treatment-emergent adverse events were injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache. During 12 months of abaloparatide treatment, men with osteoporosis exhibited rapid and significant improvements in BMD with a safety profile consistent with previous studies. These results suggest abaloparatide can be considered as an effective anabolic treatment option for men with osteoporosis. © 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Proteína Relacionada ao Hormônio Paratireóideo , Idoso , Humanos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Método Duplo-Cego , Colo do Fêmur , Osteoporose/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Masculino
5.
Arch. endocrinol. metab. (Online) ; 66(5): 707-716, Sept.-Oct. 2022. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1420079

RESUMO

ABSTRACT Anabolic agents for the treatment of osteoporosis increase bone density, improve bone strength, and reduce fracture risk. They are distinguished from antiresorptive drugs by their property of increasing osteoblastic bone formation. Teriparatide and abaloparatide are parathyroid hormone receptor agonists that increase bone remodeling with bone formation increasing more than bone resorption. Romosozumab is a humanized monoclonal antibody to sclerostin that has a "dual effect" of increasing bone formation while decreasing bone resorption. The bone forming effects of anabolic therapy appear to be self-limited, making it imperative that it be followed by antiresorptive therapy to enhance or consolidate the beneficial effects achieved. Teriparatide, abaloparatide, and romosozumab each have unique pharmacological properties that must be appreciated when using them to treat patients at high risk for fracture. Clinical trials have shown a favorable balance of expected benefits and possible risks. Anabolic therapy is superior to bisphosphonates for high-risk patients, with greater benefit when initial treatment is with an anabolic agent followed by an antiresorptive drug, rather than the reverse sequence of therapy. Recent clinical practice guidelines have included recommendations with examples of patients who are candidates with anabolic therapy.

6.
Postgrad Med ; 134(6): 541-551, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35635798

RESUMO

Reducing fracture risk is the objective of osteoporosis treatment. Bone-forming osteoporosis drugs increase bone mass, restore bone microarchitecture, and reduce fracture risk more effectively than oral bisphosphonates, providing strong justification for the use of these agents as the initial therapy or after anti-remodeling agents in patients at very high risk of fracture. At the end of a 12-to-24-month course of osteoanabolic therapy, transitioning to a potent anti-remodeling agent maintains and enhances the treatment benefit. This review describes the clinical applications of osteoanabolic therapy for osteoporosis.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Anticorpos Monoclonais/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Humanos , Osteoporose/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/efeitos adversos , Teriparatida/farmacologia
7.
Curr Osteoporos Rep ; 20(1): 1-12, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35032004

RESUMO

PURPOSE OF REVIEW: This review provides suggestions for the evaluation of patients with osteoporosis in order to assure that the diagnosis is correct, to identify potentially correctable conditions contributing to skeletal fragility and fracture risk, and to assist in individualizing management decisions. RECENT FINDINGS: Some patients who appear to have osteoporosis have another skeletal disease, such as osteomalacia, that requires further evaluation and treatment that is different than for osteoporosis. Many patients with osteoporosis have contributing factors (e.g., vitamin D deficiency, high fall risk) that should be addressed before and after starting treatment to assure that treatment is effective and safe. Evaluation includes a focused medical history, skeletal-related physical examination, assessment of falls risk, appropriate laboratory tests, and rarely transiliac double-tetracycline labeled bone biopsy. Evaluation of patients with osteoporosis before starting treatment is essential for optimizing clinical outcomes.


Assuntos
Fraturas Ósseas , Osteomalacia , Osteoporose , Deficiência de Vitamina D , Densidade Óssea , Osso e Ossos , Fraturas Ósseas/complicações , Humanos , Osteomalacia/complicações , Osteoporose/tratamento farmacológico , Deficiência de Vitamina D/complicações
8.
Biol Blood Marrow Transplant ; 26(10): 1784-1802, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32653624

RESUMO

Bone health disturbances commonly occur after hematopoietic cell transplantation (HCT) with loss of bone mineral density (BMD) and avascular necrosis (AVN) foremost among them. BMD loss is related to pretransplantation chemotherapy and radiation exposure and immunosuppressive therapy for graft-versus-host-disease (GVHD) and results from deficiencies in growth or gonadal hormones, disturbances in calcium and vitamin D homeostasis, as well as osteoblast and osteoclast dysfunction. Although the pathophysiology of AVN remains unclear, high-dose glucocorticoid exposure is the most frequent association. Various societal treatment guidelines for osteoporosis exist, but the focus is mainly on menopausal-associated osteoporosis. HCT survivors comprise a distinct population with unique comorbidities, making general approaches to bone health management inappropriate in some cases. To address a core set of 16 frequently asked questions (FAQs) relevant to bone health in HCT, the American Society of Transplant and Cellular Therapy Committee on Practice Guidelines convened a panel of experts in HCT, adult and pediatric endocrinology, orthopedics, and oral medicine. Owing to a lack of relevant prospective controlled clinical trials that specifically address bone health in HCT, the answers to the FAQs rely on evidence derived from retrospective HCT studies, results extrapolated from prospective studies in non-HCT settings, relevant societal guidelines, and expert panel opinion. Given the heterogenous comorbidities and needs of individual HCT recipients, answers to FAQs in this article should be considered general recommendations, with good medical practice and judgment ultimately dictating care of individual patients. Readers are referred to the Supplementary Material for answers to additional FAQs that did not make the core set.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Densidade Óssea , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Estados Unidos
9.
J Clin Densitom ; 23(1): 1-20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31685420

RESUMO

The 20th annual Santa Fe Bone Symposium was held August 9-10, 2019, in Santa Fe, New Mexico, USA. This is an annual meeting devoted to clinical applications of recent advances in skeletal research that impact the care of patients with osteoporosis, metabolic bone diseases, and inherited bone diseases. Participants included practicing and academic physicians, fellows, advanced practice providers, fracture liaison service (FLS) coordinators, clinical researchers, and bone density technologists. The symposium consisted of lectures, case presentations, and panel discussions, with an emphasis on learning through interaction of all attendees. Topics included new approaches in the use of anabolic agents for the treatment osteoporosis, a review of important events in skeletal health over the past year, new and emerging treatments for rare bone diseases, the use of genetic testing for bone diseases in clinical practice, medication-associated causes of osteoporosis, new concepts in the use of estrogen therapy for osteoporosis, new Official Positions of the International Society for Clinical Densitometry, skeletal consequences of bariatric surgery, and update on the progress and potential of Bone Health TeleECHO, a virtual community of practice using videoconferencing technology to link healthcare professionals for advancing the care of osteoporosis worldwide. Sessions on rare bone diseases were developed in collaboration with the Rare Bone Disease Alliance. Symposium premeetings included an FLS workshop by the National Osteoporosis Foundation and others devoted to the use of new therapeutic agents for the care of osteoporosis and related disorders.


Assuntos
Doenças Ósseas/terapia , Osteoporose/terapia , Animais , Densidade Óssea , Doenças Ósseas/genética , Doenças Ósseas/metabolismo , Humanos , Doenças Raras/terapia
10.
J Clin Densitom ; 22(4): 453-471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31400968

RESUMO

To answer important questions in the fields of monitoring with densitometry, dual-energy X-ray absorptiometry machine cross-calibration, monitoring, spinal cord injury, periprosthetic and orthopedic bone health, transgender medicine, and pediatric bone health, the International Society for Clinical Densitometry (ISCD) held a Position Development Conference from March 20 to 23, 2019. Potential topics requiring guidance were solicited from ISCD members in 2017. Following that, a steering committee selected, prioritized, and grouped topics into Task Forces. Chairs for each Task Force were appointed and the members were co-opted from suggestions by the Steering Committee and Task Force Chairs. The Task Forces developed key questions, performed literature searches, and came up with proposed initial positions with substantiating draft publications, with support from the Steering Committee. An invited Panel of Experts first performed a review of draft positions using a modified RAND Appropriateness Method with voting for appropriateness. Draft positions deemed appropriate were further edited and presented at the Position Development Conference meeting in an open forum. A second round of voting occurred after discussions to approve or reject the positions. Finally, a face-to-face closed session with experts and Task Force Chairs, and subsequent electronic follow-up resulted in 34 Official Positions of the ISCD approved by the ISCD Board on May 28, 2019. The Official Positions and the supporting evidence were submitted for publication on July 1, 2019. This paper provides a summary of the all the ISCD Adult and Pediatric Official Positions, with the new 2019 positions highlighted in bold.


Assuntos
Absorciometria de Fóton/normas , Densidade Óssea , Conferências de Consenso como Assunto , Fraturas Periprotéticas/diagnóstico , Traumatismos da Medula Espinal/diagnóstico , Pessoas Transgênero , Criança , Feminino , Humanos , Masculino , Fraturas Periprotéticas/terapia , Sociedades Médicas , Traumatismos da Medula Espinal/terapia
11.
J Clin Densitom ; 22(4): 484-488, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31375350

RESUMO

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with a decline in quality of life and high morbidity and mortality. The presence of a VF is a significant risk factor for developing another fracture; however, most VFs are not clinically recognized and diagnosed. Vertebral fracture assessment by dual-energy X-ray absorptiometry is a low cost, low radiation, convenient, and reliable method to identify VFs. The finding of a previously unrecognized VF may change the assessment of fracture risk, diagnostic classification, and treatment strategies. Vertebral fracture assessment or radiographic lateral spine imaging should be repeated in patients with continued high risk for fracture (e.g., historical height loss >4 cm [>1.5 inches], self-reported but undocumented vertebral fracture, or glucocorticoid therapy equivalent to ≥5 mg of prednisone or equivalent per day for greater than or equal to 3 months).


Assuntos
Absorciometria de Fóton/normas , Conferências de Consenso como Assunto , Fraturas por Osteoporose/diagnóstico , Fraturas da Coluna Vertebral/diagnóstico , Humanos , Recidiva
12.
JAMA Surg ; 154(11): 1078, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389993
13.
J Clin Densitom ; 22(1): 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30366683

RESUMO

The Santa Fe Bone Symposium is an annual meeting devoted to clinical applications of recent advances in skeletal research. The 19th Santa Fe Bone Symposium convened August 3-4, 2018, in Santa Fe, New Mexico, USA. Attendees included physicians of many specialties, fellows in training, advanced practice providers, clinical researchers, and bone density technologists. The format consisted of lectures, case presentations by endocrinology fellows, and panel discussions, with all involving extensive interactive discussions. Topics were diverse, including an evolutionary history of calcium homeostasis, osteoporosis treatment in the very old, optimizing outcomes with orthopedic surgery, microbiome and bone, new strategies for combination and sequential therapy of osteoporosis, exercise as medicine, manifestations of parathyroid hormone excess and deficiency, parathyroid hormone as a therapeutic agent, cell senescence and bone health, and managing patients outside clinical practice guidelines. The National Bone Health Alliance conducted a premeeting on development of fracture liaison services. A workshop was devoted to Bone Health TeleECHO (Bone Health Extension for Community Healthcare Outcomes), a strategy of ongoing medical education for healthcare professions to expand capacity to deliver best practice skeletal healthcare in underserved communities and reduce the osteoporosis treatment gap.


Assuntos
Terapia por Exercício , Fraturas Espontâneas/terapia , Osteoporose/fisiopatologia , Osteoporose/terapia , Hormônio Paratireóideo/farmacologia , Fraturas da Coluna Vertebral/terapia , Fatores Etários , Animais , Remodelação Óssea , Osso e Ossos/metabolismo , Senescência Celular , Consolidação da Fratura/efeitos dos fármacos , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/prevenção & controle , Humanos , Microbiota/fisiologia , Uso Off-Label , Osteoporose/complicações , Hormônio Paratireóideo/uso terapêutico , Guias de Prática Clínica como Assunto , Probióticos/uso terapêutico , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia , Fusão Vertebral
14.
Ther Adv Musculoskelet Dis ; 10(11): 209-223, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30386439

RESUMO

Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL), a cytokine expressed by cells of the osteoblast lineage that is a key regulator of osteoclastic bone resorption. By binding and neutralizing RANKL, denosumab inhibits osteoclast differentiation, activity, and survival. Clinical trials in postmenopausal women with osteoporosis have shown that it reduces the risk of vertebral fractures, nonvertebral fractures, and hip fractures, with a generally favorable safety profile. With a dose of 60 mg subcutaneously every 6 months, it is approved for: treatment of postmenopausal women and men with osteoporosis, and for women and men with glucocorticoid-induced osteoporosis who are at high risk for fracture; treatment to increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer; and treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. Atypical femur fractures and osteonecrosis of the jaw have been reported in patients treated with denosumab. Discontinuation of denosumab is followed by rapidly rising bone turnover markers, decreasing bone density, and vertebral fracture risk that returns to baseline, with a possible increase in the risk of multiple vertebral fractures. Further study is needed to clarify this potential risk. After stopping long-term denosumab, patients should be switched to another antiresorptive agent to maintain the benefit achieved with denosumab.

15.
Calcif Tissue Int ; 103(5): 540-545, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29951742

RESUMO

Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 signaling pathway. In the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fracture compared with placebo and of major osteoporotic fracture compared with teriparatide. To further evaluate the effectiveness of ABL, we calculated the number needed to treat (NNT) to prevent one fracture using ACTIVE data. To estimate the potential effectiveness of ABL in populations at higher fracture risk than in ACTIVE, we calculated NNT for vertebral fracture using reference populations from historical placebo-controlled trials, assuming an 86% relative risk reduction in vertebral fracture with ABL treatment as observed in ACTIVE. NNT was calculated as the reciprocal of the absolute risk reduction in ACTIVE. The projected NNT for ABL in other populations was calculated based on incidence rate (IR) for vertebral fractures in the placebo arms of the FREEDOM (placebo IR 7.2%), FIT-1 (placebo IR 15.0%), and FIT-2 (placebo IR 3.8%) trials. NNT for ABL in ACTIVE was 28 for vertebral, 55 for nonvertebral, 37 for clinical, and 34 for major osteoporotic fracture. NNT for these fracture types for teriparatide in ACTIVE were 30, 92, 59, and 75, respectively. Using placebo IRs from FREEDOM, FIT-1, and FIT-2, projected NNTs for vertebral fracture with ABL were 17, 8, and 31. These data are useful for further evaluating ABL for the treatment of osteoporosis in postmenopausal women.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Teriparatida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Projetos de Pesquisa
16.
J Bone Miner Res ; 33(2): 298-306, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29024120

RESUMO

There has been renewed interest of late in the role of modeling-based formation (MBF) during osteoporosis therapy. Here we describe early effects of an established anabolic (teriparatide) versus antiresorptive (denosumab) agent on remodeling-based formation (RBF), MBF, and overflow MBF (oMBF) in human transiliac bone biopsies. Postmenopausal women with osteoporosis received subcutaneous teriparatide (n = 33, 20 µg/d) or denosumab (n = 36, 60 mg once/6 months), open-label for 6 months at 7 US and Canadian sites. Subjects received double fluorochrome labeling at baseline and before biopsy at 3 months. Sites of bone formation were designated as MBF if the underlying cement line was smooth, RBF if scalloped, and oMBF if formed over smooth cement lines adjacent to scalloped reversal lines. At baseline, mean RBF/bone surface (BS), MBF/BS, and oMBF/BS were similar between the teriparatide and denosumab groups in each bone envelope assessed (cancellous, endocortical, periosteal). All types of formation significantly increased from baseline in the cancellous and endocortical envelopes (differences p < 0.001) with teriparatide (range of changes 2.9- to 21.9-fold), as did MBF in the periosteum (p < 0.001). In contrast, all types of formation were decreased or not significantly changed with denosumab, except MBF/BS in the cancellous envelope, which increased 2.5-fold (difference p = 0.048). These data highlight mechanistic differences between these agents: all 3 types of bone formation increased significantly with teriparatide, whereas formation was predominantly decreased or not significantly changed with denosumab, except for a slight increase in MBF/BS in the cancellous envelope. © 2017 American Society for Bone and Mineral Research.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Denosumab/farmacologia , Osteogênese/efeitos dos fármacos , Teriparatida/farmacologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade
17.
Expert Opin Emerg Drugs ; 22(3): 247-257, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28756709

RESUMO

INTRODUCTION: Osteoporosis is a common skeletal disease with serious consequences due to osteoporotic fractures and high costs to society for post-fracture care. Most patients at high risk for fracture are not receiving care to reduce fracture risk. The osteoporosis treatment gap has reached crisis proportions. Strategies to reduce the treatment gap include systematic methods for identifying and treating high risk patients, better education of patients and healthcare providers, better use of currently available drugs, and development of new drugs to treat osteoporosis. Areas covered: Two osteoanabolic agents with novel mechanisms of action have recently completed phase 3 clinical trials. The efficacy and safety findings of these studies are reviewed. Abaloparatide, a synthetic analog of parathyroid hormone-related protein, has received regulatory approval for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Romosozumab, a humanized monoclonal antibody to sclerostin, an endogenous inhibitor of bone formation, is under regulatory review. Expert opinion: Osteoanabolic therapy for osteoporosis can restore, at least in part, the degradation of bone microarchitecture that is a hallmark of this disease. The emergence of new osteoanabolic compounds expands the treatment options for patients at high risk for fracture.


Assuntos
Anabolizantes/uso terapêutico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Anabolizantes/efeitos adversos , Anabolizantes/farmacologia , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Desenho de Fármacos , Humanos , Osteoporose/complicações , Osteoporose/patologia , Proteína Relacionada ao Hormônio Paratireóideo/efeitos adversos , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Educação de Pacientes como Assunto
18.
J Bone Miner Res ; 32(10): 1977-1980, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28731215

RESUMO

Hypophosphatasia (HPP) is a rare inherited disorder of bone affecting approximately 500 to 600 known individuals in the United States. HPP is the result of mutations involving the gene for tissue nonspecific alkaline phosphatase. Five clinical types of HPP are recognized. The clinical presentation of HPP varies from devastating prenatal intrauterine disease to mild manifestations in adulthood. In adults, main clinical involvement includes early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, and fractures. Treatment for HPP is limited. Asfotase alfa is a subcutaneously administered synthetic human alkaline phosphatase that is approved for treatment of patients, including adults, with perinatal/infantile- and juvenile-onset HPP. However, guidelines for the treatment of adults with HPP are not available. This discussion addresses diagnostic and treatment considerations for adults with HPP. © 2017 American Society for Bone and Mineral Research.


Assuntos
Hipofosfatasia/patologia , Hipofosfatasia/terapia , Adulto , Humanos , Hipofosfatasia/diagnóstico , Resultado do Tratamento
19.
J Bone Miner Res ; 32(7): 1481-1485, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28277603

RESUMO

Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL) that decreases osteoclast formation, function and survival, and is approved for the treatment of postmenopausal women with osteoporosis at increased or high risk for fracture, among other indications. During the pivotal 3-year fracture trial FREEDOM, denosumab 60 mg subcutaneously every 6 months significantly reduced new vertebral (68%), hip (40%), and nonvertebral (20%) fractures; increased bone mineral density (BMD); and reduced bone turnover markers compared with placebo in postmenopausal women with osteoporosis. Questions have arisen regarding imbalances of certain low-frequency adverse events (AEs) observed in FREEDOM, as well as the top 5 most frequent adverse reactions listed in the United States prescribing information (USPI; back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis). We examined the incidences of these AEs in women who originally received placebo during FREEDOM and then received denosumab for up to 3 years during the FREEDOM Extension (Crossover Group). This provided a unique opportunity for comparison with the original 3-year denosumab FREEDOM observations. We also examined the incidences of these AEs over 6 years of denosumab treatment (Long-term Group; ie, comparing a second 3 years of treatment with findings in the first 3 years). There was no indication of increasing trends regarding the imbalances of either low-frequency AEs or common AEs observed in FREEDOM. © 2017 American Society for Bone and Mineral Research.


Assuntos
Denosumab/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Denosumab/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Estados Unidos/epidemiologia
20.
J Clin Densitom ; 20(2): 134-152, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28185765

RESUMO

The Santa Fe Bone Symposium is an annual meeting of healthcare professionals and clinical researchers that details the clinical relevance of advances in knowledge of skeletal diseases. The 17th Santa Fe Bone Symposium was held in Santa Fe, New Mexico, USA, on August 5-6, 2016. The program included plenary lectures, oral presentations by endocrinology fellows, meet-the-professor sessions, and panel discussions, all aimed to provide ample opportunity for interactive discussions among all participants. Symposium topics included recent developments in the translation of basic bone science to patient care, new clinical practice guidelines for postmenopausal osteoporosis, management of patients with disorders of phosphate metabolism, new and emerging treatments for rare bone diseases, strategies to enhance fracture healing, and an update on Bone Health Extension for Community Healthcare Outcomes, using a teleconferencing platform to elevate the level of knowledge of healthcare professionals in underserved communities to deliver best practice care for skeletal diseases. The highlights and important clinical messages of the 2016 Santa Fe Bone Symposium are provided herein by each of the faculty presenters.


Assuntos
Absorciometria de Fóton , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Fósforo/sangue , Doenças Raras/tratamento farmacológico , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/diagnóstico por imagem , Catepsina K/antagonistas & inibidores , Doença Crônica , Denosumab/uso terapêutico , Descoberta de Drogas , Consolidação da Fratura , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/tratamento farmacológico , Hipofosfatemia/sangue , Hipofosfatemia/diagnóstico , Hipofosfatemia/tratamento farmacológico , Hipofosfatemia/etiologia , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Guias de Prática Clínica como Assunto , Ligante RANK/metabolismo , Doenças Raras/sangue , Doenças Raras/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Pesquisa Translacional Biomédica
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