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1.
Inorg Chem ; 63(14): 6493-6499, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38517353

ABSTRACT

The electronic structure of the bis(dioxolene) bridging ligand -SQ2Th2- is responsive to metal-ligand magnetic exchange coupling. Comparison of the crystal structure of (NiSQ)2Th2 to that of (ZnSQ)2Th2 indicates an open-shell biradical ground state for the dinuclear Ni(II) complex compared to the closed-shell quinoidal character found in the dinuclear Zn(II) complex. Consistent with a comparison of bond lengths obtained by X-ray diffraction, the analysis of the variable-temperature magnetic susceptibility data for crystalline (NiSQ)2Th2 yields reduced SQ-SQ radical-radical magnetic exchange coupling (JSQ-SQ = -203 cm-1) compared to that of (ZnSQ)2Th2 (JSQ-SQ = -321 cm-1). The reduced SQ-SQ exchange coupling in (NiSQ)2Th2 derives from an attenuation of the SQ spin densities, which in turn is derived from the Ni-SQ antiferromagnetic exchange interactions. This reduction in SQ--SQ exchange that we observe for (NiSQ)2Th2 correlates with an effective lengthening of the bridge unit by ∼2.1 Šrelative to that of (ZnSQ)2Th2. This magnitude of the effective increase in the bridge distance is consistent with the (NiSQ)2Th2 JSQ-SQ value lying between those of (ZnSQ)2Th2 and (ZnSQ)2Th3. The ability to modulate spin populations on an organic radical via pairwise Ni-SQ magnetic exchange interactions is a general way to affect electronic coupling in the Th-Th bridge. Our results suggest that metal-radical exchange coupling represents a powerful mechanism for tuning organic molecular electronic structure, with important implications for molecular electronics and molecular electron transport.

2.
J Clin Densitom ; 25(4): 649-667, 2022.
Article in English | MEDLINE | ID: mdl-36280582

ABSTRACT

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.


Subject(s)
Bone Diseases, Metabolic , Osteoporosis , Osteoporotic Fractures , Humans , Absorptiometry, Photon , Osteoporosis/drug therapy , Bone Diseases, Metabolic/therapy , Osteoporotic Fractures/prevention & control
3.
J Clin Densitom ; 25(1): 3-19, 2022.
Article in English | MEDLINE | ID: mdl-34785102

ABSTRACT

The 2021 Virtual Santa Fe Bone Symposium was held August 5-8, with over 300 registered attendees from throughout the USA, and at least 18 other countries. This annual meeting focuses on applying advances in basic science and clinical research to the care of patients with osteoporosis and those with inherited and acquired disorders of bone metabolism. Participants represented a broad range of medical disciplines with an interest in skeletal diseases. These included physicians of many specialties and practice settings, fellows, advanced practice providers, fracture liaison service (FLS) coordinators, clinical researchers, and bone density technologists. There were lectures, case presentations, and panel discussions, all followed by interactive discussions. Breakout sessions included an FLS workshop, Bone Health TeleECHO workshop, special interest groups, meet-and-greet the faculty, and satellite symposia. The agenda covered topics of interest such as strategies for the use of osteoanabolic therapy, prevention of periprosthetic fractures, management of atypical femur fractures, what we know and don't know about vitamin D, advances in the use of dual-energy X-ray absorptiometry in the assessment of skeletal health, controversies and conundrums in osteoporosis care, skeletal health in transgender patients, management of patients with hypophosphatasia and hypophosphatemia, and treat-to-target approaches for managing patients with osteoporosis. The Proceedings of the 2021 Virtual Santa Fe Bone Symposium consists of highlights of each presentation with current strategies for optimizing the care of patients with skeletal disorders.


Subject(s)
Bone Density Conservation Agents , Bone Diseases, Metabolic , Osteoporosis , Osteoporotic Fractures , Absorptiometry, Photon , Bone Density , Bone Density Conservation Agents/therapeutic use , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/therapy , Bone and Bones , Humans , Osteoporosis/drug therapy , Osteoporotic Fractures/prevention & control
4.
Am J Kidney Dis ; 78(4): 582-589, 2021 10.
Article in English | MEDLINE | ID: mdl-33774081

ABSTRACT

Osteoporosis is defined as a skeletal disorder of compromised bone strength predisposing those affected to an elevated risk of fracture. However, based on bone histology, osteoporosis is only part of a spectrum of skeletal complications that includes osteomalacia and the various forms of renal osteodystrophy of chronic kidney disease-mineral and bone disorder (CKD-MBD). In addition, the label "kidney-induced osteoporosis" has been proposed, even though the changes caused by CKD do not qualify as osteoporosis by the histological diagnosis. It is clear, therefore, that such terminology may not be helpful diagnostically or in making treatment decisions. A new label, "CKD-MBD/osteoporosis" could be a more appropriate term because it brings osteoporosis under the official label of CKD-MBD. Neither laboratory nor noninvasive diagnostic investigations can discriminate osteoporosis from the several forms of renal osteodystrophy. Transiliac crest bone biopsy can make the diagnosis of osteoporosis by exclusion of other kidney-associated bone diseases, but its availability is limited. Recently, a classification of metabolic bone diseases based on bone turnover, from low to high, together with mineralization and bone volume, has been proposed. Therapeutically, no antifracture treatments have been approved by the US Food and Drug Administration for patients with kidney-associated bone disease. Agents that suppress parathyroid hormone (vitamin D analogues and calcimimetics) are used to treat hyperparathyroid bone disease. Antiresorptive and osteoanabolic agents approved for osteoporosis are being used off-label to treat CKD stages 3b-5 in high-risk patients. It has now been suggested that intermittent administration of parathyroid hormone as early as CKD stage 2 could be an effective management strategy. If confirmed in clinical trials, it could mitigate the retention of phosphorus and subsequently the rise in fibroblast growth factor 23 and may be beneficial for coexisting osteoporosis.


Subject(s)
Chronic Kidney Disease-Mineral and Bone Disorder/epidemiology , Chronic Kidney Disease-Mineral and Bone Disorder/metabolism , Osteoporosis/epidemiology , Osteoporosis/metabolism , Anabolic Agents/pharmacology , Anabolic Agents/therapeutic use , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/metabolism , Bone Diseases, Metabolic/therapy , Bone Remodeling/drug effects , Bone Remodeling/physiology , Chronic Kidney Disease-Mineral and Bone Disorder/therapy , Fibroblast Growth Factor-23 , Humans , Hyperparathyroidism/blood , Hyperparathyroidism/epidemiology , Hyperparathyroidism/metabolism , Hyperparathyroidism/therapy , Osteoporosis/therapy , Parathyroid Hormone/metabolism , Vitamin D/pharmacology , Vitamin D/therapeutic use
6.
J Clin Densitom ; 23(1): 1-20, 2020.
Article in English | MEDLINE | ID: mdl-31685420

ABSTRACT

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.


Subject(s)
Bone Diseases/therapy , Osteoporosis/therapy , Animals , Bone Density , Bone Diseases/genetics , Bone Diseases/metabolism , Humans , Rare Diseases/therapy
7.
J Clin Densitom ; 22(1): 1-19, 2019.
Article in English | MEDLINE | ID: mdl-30366683

ABSTRACT

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.


Subject(s)
Exercise Therapy , Fractures, Spontaneous/therapy , Osteoporosis/physiopathology , Osteoporosis/therapy , Parathyroid Hormone/pharmacology , Spinal Fractures/therapy , Age Factors , Animals , Bone Remodeling , Bone and Bones/metabolism , Cellular Senescence , Fracture Healing/drug effects , Fractures, Spontaneous/etiology , Fractures, Spontaneous/prevention & control , Humans , Microbiota/physiology , Off-Label Use , Osteoporosis/complications , Parathyroid Hormone/therapeutic use , Practice Guidelines as Topic , Probiotics/therapeutic use , Risk Factors , Spinal Fractures/etiology , Spinal Fusion
8.
Calcif Tissue Int ; 102(6): 627-633, 2018 06.
Article in English | MEDLINE | ID: mdl-29285549

ABSTRACT

Geographic heterogeneity has been observed in fracture risk and efficacy of therapeutic intervention in postmenopausal osteoporosis. The objectives of these analyses were to assess across geographic and ethnic subgroups the heterogeneity of fracture incidence and baseline risk, and consistency of effect of abaloparatide-SC vs placebo on fracture risk reduction in the 18-month, phase 3, multinational, ACTIVE randomized controlled trial. Prespecified exploratory analyses of geographic subgroups (North America, South America, Europe, Asia) and post hoc analyses of ethnic subgroups (Hispanic or Latino, other) of postmenopausal women with osteoporosis enrolled in the abaloparatide-SC and placebo cohorts (n = 1645) were performed. Country-specific FRAX models were used to calculate 10-year absolute fracture risks. Relative risk reductions for vertebral fractures and hazard ratios for non-vertebral, clinical, and major osteoporotic fractures were calculated. Forest plots were constructed to assess treatment-by-subgroup interactions for each geographic region and ethnicity. Baseline prevalence of vertebral fractures was similar across geographies; baseline prevalence of non-vertebral fractures was more variable. Ten-year major osteoporosis fracture and hip fracture risks were variable across and within regions. The effects of abaloparatide-SC on reducing the risk of vertebral, non-vertebral, clinical, and major osteoporotic fractures were similar across regions, and for Hispanic or Latino vs other ethnicities. A limitation was the limited power to detect interactions with few events. In conclusion, despite geographic variability in fracture incidence and risk at baseline, no differences were detected in the effects of abaloparatide-SC in reducing vertebral, non-vertebral, clinical, and major osteoporotic fracture risk across assessed geographic regions and ethnicities.


Subject(s)
Osteoporosis, Postmenopausal/prevention & control , Osteoporotic Fractures/prevention & control , Parathyroid Hormone-Related Protein/pharmacology , Aged , Aged, 80 and over , Bone Density Conservation Agents/pharmacology , Female , Humans , Incidence , Middle Aged , Osteoporosis, Postmenopausal/epidemiology , Osteoporotic Fractures/epidemiology , Postmenopause , Spinal Fractures/drug therapy , Treatment Outcome
9.
Calcif Tissue Int ; 102(6): 634, 2018 06.
Article in English | MEDLINE | ID: mdl-29383409

ABSTRACT

The article Geography of Fracture Incidence in Postmenopausal Women with Osteoporosis Treated with Abaloparatide, written by Michael R. McClung, Gregory C. Williams, Gary Hattersley, Lorraine A. Fitzpatrick, Yamei Wang, Paul D. Miller, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 28 December 2017 without open access.

10.
J Clin Densitom ; 21(1): 3-21, 2018.
Article in English | MEDLINE | ID: mdl-29229501

ABSTRACT

The 18th Annual Santa Fe Bone Symposium was held on August 4-5, 2017, in Santa Fe, New Mexico, USA. The symposium convenes health-care providers and clinical researchers to present and discuss clinical applications of recent advances in research of skeletal diseases. The program includes lectures, oral presentations by endocrinology fellows, case-based panel discussions, and breakout sessions on topics of interest, with emphasis on participation and interaction of all participants. Topics included the evaluation and treatment of adult survivors with pediatric bone diseases, risk assessment and management of atypical femur fractures, nonpharmacologic strategies in the care of osteoporosis, and skeletal effects of parathyroid hormone with opportunities for therapeutic intervention. Management of skeletal complications of rheumatic diseases was discussed. Insights into sequential and combined use of antiresorptive agents were presented. Individualization of patient treatment decisions when clinical practice guidelines may not be applicable was covered. Challenges and opportunities with osteoporosis drug development were discussed. There was an update on progress of Bone Health TeleECHO (Bone Health Extension for Community Healthcare Outcomes), a teleconferencing strategy for sharing knowledge and expanding capacity to deliver best-practice skeletal health care.


Subject(s)
Diphosphonates/therapeutic use , Osteoporosis/drug therapy , Accidental Falls/prevention & control , Diet , Diphosphonates/adverse effects , Drug Development , Exercise , Humans , Life Style , Osteoporosis/complications , Osteoporosis/therapy , Osteoporotic Fractures/etiology , Rheumatic Diseases/complications
11.
J Clin Densitom ; 20(2): 134-152, 2017.
Article in English | MEDLINE | ID: mdl-28185765

ABSTRACT

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.


Subject(s)
Absorptiometry, Photon , Bone Density Conservation Agents/therapeutic use , Bone Diseases, Metabolic/drug therapy , Osteoporotic Fractures/drug therapy , Phosphorus/blood , Rare Diseases/drug therapy , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/diagnostic imaging , Cathepsin K/antagonists & inhibitors , Chronic Disease , Denosumab/therapeutic use , Drug Discovery , Fracture Healing , Humans , Hyperphosphatemia/blood , Hyperphosphatemia/drug therapy , Hypophosphatemia/blood , Hypophosphatemia/diagnosis , Hypophosphatemia/drug therapy , Hypophosphatemia/etiology , Osteoporosis/diagnostic imaging , Osteoporosis/drug therapy , Parathyroid Hormone-Related Protein/therapeutic use , Practice Guidelines as Topic , RANK Ligand/metabolism , Rare Diseases/blood , Rare Diseases/genetics , Receptor Activator of Nuclear Factor-kappa B/metabolism , Translational Research, Biomedical
12.
Endocr Pract ; 22(9): 1111-8, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27643923

ABSTRACT

ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX(®) = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization.


Subject(s)
Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/therapy , Biomarkers/blood , Bone Density , Collagen Type I/blood , Endocrinology/organization & administration , Endocrinology/standards , Evidence-Based Practice , Humans , Osteoporotic Fractures/diagnosis , Osteoporotic Fractures/therapy , Parathyroid Hormone/blood , Societies, Medical/organization & administration , Societies, Medical/standards , United States , Vitamin D/analogs & derivatives , Vitamin D/blood
13.
Endocr Pract ; 22(Suppl 4): 1-42, 2016 Sep 02.
Article in English | MEDLINE | ID: mdl-27662240

ABSTRACT

ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX® = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization.


Subject(s)
Endocrinology/standards , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/therapy , Absorptiometry, Photon , Bone Density , Endocrinologists/standards , Fractures, Bone/diagnosis , Fractures, Bone/epidemiology , Fractures, Bone/prevention & control , Humans , Osteoporosis, Postmenopausal/epidemiology , Societies, Medical/organization & administration , Societies, Medical/standards , United States/epidemiology
14.
J Clin Densitom ; 19(1): 97-101, 2016.
Article in English | MEDLINE | ID: mdl-26439186

ABSTRACT

Vertebral compression fractures (VCF's) are the most common form of osteoporotic fractures. Whether symptomatic or asymptomatic, they both represent a high risk for not only vertebral but also nonvertebral fractures in untreated populations. This high risk of future fracture after a VCF is independent of the T-score because bone strength is a combination of bone mineral density and bone quality. VCFs are the single greatest risk for future fractures at all other skeletal sites in untreated populations, including hip fractures. They are often unrecognized despite their exceptionally high prevalence in all genders and most ethnic groups as age increases. This article highlights some of the key messages about VCF's, and how assessment for their presence and then management will reduce the risk of all osteoporotic fractures.


Subject(s)
Fractures, Compression/therapy , Spinal Fractures/therapy , Fractures, Compression/diagnosis , Humans , Spinal Fractures/diagnosis
15.
J Clin Densitom ; 19(1): 102-16, 2016.
Article in English | MEDLINE | ID: mdl-26750746

ABSTRACT

The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities.


Subject(s)
Bone Diseases, Metabolic , Osteoporosis , California , Humans
16.
JAMA ; 316(7): 722-33, 2016 Aug 16.
Article in English | MEDLINE | ID: mdl-27533157

ABSTRACT

IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 µg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 µg (n = 824); or open-label teriparatide, 20 µg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004.


Subject(s)
Lumbar Vertebrae/injuries , Osteoporosis, Postmenopausal , Osteoporotic Fractures/prevention & control , Parathyroid Hormone-Related Protein/therapeutic use , Spinal Fractures/prevention & control , Thoracic Vertebrae/injuries , Aged , Aged, 80 and over , Bone Density/drug effects , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Double-Blind Method , Female , Femur Neck/diagnostic imaging , Femur Neck/physiology , Humans , Hypercalcemia/chemically induced , Injections, Subcutaneous , Lumbar Vertebrae/physiopathology , Middle Aged , Parathyroid Hormone-Related Protein/adverse effects , Pelvic Bones/drug effects , Pelvic Bones/physiology , Placebos/therapeutic use , Postmenopause , Radiography , Teriparatide/adverse effects , Teriparatide/therapeutic use
17.
Am J Kidney Dis ; 65(6): 933-6, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25843705

ABSTRACT

Teriparatide, a recombinant form of parathyroid hormone, is an anabolic agent approved for use in women and men with osteoporosis. However, it is not well studied in people with chronic kidney disease (CKD). We report on a patient with stage 5 CKD treated with dialysis who presented to our clinic with multiple fractures, including bilateral nondisplaced pelvic fractures resulting in chronic pain and interfering with the patient's ability to work. Bone histomorphometry demonstrated low-turnover bone disease, and he was treated with 20µg of teriparatide (subcutaneous injection) every morning for 24 months. Within 6 months of initiating therapy, the patient's pain resolved and he was able to resume work. Serum calcium and phosphate levels remained within reference ranges throughout his treatment, and he sustained no further fractures. During 24 months of treatment, bone mineral density was maintained at the lumbar spine, and there was an increase of 4% at the femoral neck and total hip. A second transiliac bone biopsy demonstrated improvements in static and dynamic parameters of bone formation. In our patient, 24-month treatment with teriparatide was safe and effective; however, larger studies are needed to determine the efficacy of teriparatide in the dialysis-dependent CKD population.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Diseases, Metabolic/drug therapy , Kidney Failure, Chronic/therapy , Renal Dialysis , Teriparatide/therapeutic use , Adult , Bone Diseases, Metabolic/etiology , Fractures, Bone/etiology , Humans , Kidney Failure, Chronic/complications , Male
18.
Endocr Res ; 40(2): 106-19, 2015.
Article in English | MEDLINE | ID: mdl-25803304

ABSTRACT

The 2014 Santa Fe Bone Symposium provided a setting for the presentation and discussion of the clinical relevance of recent advances in the fields of osteoporosis and metabolic bone disease. The format included oral presentations of abstracts by endocrinology fellows, plenary lectures, panel discussions and breakout sessions, with ample opportunities for informal discussions before and after scheduled events. Topics addressed in these proceedings included a review of the important scientific publications in the past year, fracture prevention in patients with dysmobility and immobility, fracture liaison services for secondary fracture prevention, management of pre-menopausal osteoporosis, the role of bone microarchitecture in determining bone strength, measurement of microarchitecture in clinical practice and methods to improve the quality of bone density testing. This is a report of the proceedings of the 2014 Santa Fe Bone Symposium.


Subject(s)
Bone and Bones , Endocrinology/organization & administration , Endocrinology/trends , Osteoporosis , Absorptiometry, Photon , Bone Density , Bone and Bones/physiology , Female , Fractures, Bone/etiology , Fractures, Bone/therapy , Humans , Osteoporosis/complications , Osteoporosis/diagnosis , Osteoporosis/therapy , Osteoporosis, Postmenopausal/therapy
19.
Am J Kidney Dis ; 64(2): 290-304, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24726630

ABSTRACT

Osteoporosis is defined as a condition of impairment in bone strength due to low bone mineral density and poor bone quality and predisposes individuals to an increased risk of fractures. Osteoporosis may coexist with chronic kidney disease-mineral and bone disorder (CKD-MBD) and osteoporotic fractures occur in all stages of CKD. Management of osteoporosis in CKD should consider the pathophysiology of both disorders. Diagnosis and management of osteoporosis in patients with stages 1-3 CKD and patients without CKD are similar, but diagnosis and management decisions differ greatly once patients have stages 4-5 CKD. Discriminating between osteoporosis and CKD-MBD is best accomplished with quantitative bone histomorphometry. Biochemical markers, especially intact parathyroid hormone and bone-specific alkaline phosphatase, also may be helpful. When the diagnosis of osteoporosis is established, management in stages 4-5 CKD may include antiresorptive or anabolic agents, though evidence for efficacy is marginal in advanced CKD.


Subject(s)
Osteoporosis/diagnosis , Osteoporosis/therapy , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/therapy , Bone Density/physiology , Bone Diseases/complications , Bone Diseases/diagnosis , Bone Diseases/therapy , Disease Management , Humans , Male , Middle Aged , Osteoporosis/complications , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/trends , Renal Insufficiency, Chronic/complications
20.
Curr Osteoporos Rep ; 12(2): 227-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24659466

ABSTRACT

Dual-energy X-ray absorptiometry (DXA) is an inexpensive, noninvasive, widely available method for diagnosing osteoporosis, assessing fracture risk, and monitoring the effects of therapy. By diagnosing high-risk patients before a fracture occurs, clinicians can intervene early to reduce fracture risk. Appropriate use of DXA results in money saving for healthcare systems that might otherwise be spent for fracture-related care. Recent reports of studies evaluating DXA screening criteria and intervals for retesting have received considerable media coverage, sometimes suggesting that DXA is expensive, over-utilized, and unnecessary. This may lead to more patients who might benefit from early detection of osteoporosis remaining undiagnosed. We advocate for the use of current clinical practice guidelines with individualization of patient care factors to determine the optimal intervals for DXA testing.


Subject(s)
Absorptiometry, Photon/statistics & numerical data , Bone Density , Mass Media , Mass Screening/statistics & numerical data , Osteoporosis/diagnostic imaging , Practice Guidelines as Topic , Humans , Osteoporosis/diagnosis
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