The Journal of clinical endocrinology and metabolism, Jan 9, 2016
Denosumab-induced parathyroid hormone (PTH) elevation may stimulate early bone formation. Evaluat... more Denosumab-induced parathyroid hormone (PTH) elevation may stimulate early bone formation. Evaluate whether denosumab-induced changes of intact (i)PTH result in early anabolic effects according to histomorphometry and bone turnover markers (BTM) compared with teriparatide, an established anabolic agent. This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months. United States and Canadian sites. Sixty-nine postmenopausal women with osteoporosis. Teriparatide (20 μg/day) for 6 months; denosumab (60 mg once). Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface (MS/BS); histomorphometric indices in 4 bone envelopes; BTM and iPTH at baseline, 1, 3, and 6 months. After denosumab, iPTH peaked at month 1 (P<0.001) then declined, remaining above baseline through month 6 (P≤0.01); after teriparatide, iPTH declined at all timepoints (P<0.001). From ba...
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry, Jan 29, 2015
The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researcher... more 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.
Advanced age is an important risk factor for fracture. The Abaloparatide Comparator Trial In Vert... more Advanced age is an important risk factor for fracture. The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) trial showed that subcutaneous abaloparatide increased bone mineral density (BMD) and reduced the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. This study describes the effects of abaloparatide in the subgroup of women aged 80 or more years in ACTIVE. Post hoc analyses of BMD and fracture incidence in this subgroup of women who received abaloparatide or placebo in the 18-month, phase 3, double-blind, randomized controlled ACTIVE trial. The mean ages of the women ≥80 years were 81.9 and 81.7 years in the placebo (n = 43) and abaloparatide (n = 51) groups, respectively. The increases in BMD from baseline to 18 months with abaloparatide treatment were 3.9% at the total hip (P < 0.001), 3.6% at the femoral neck (P < 0.01), and 12.1% at the lumbar spine (P < 0.001), and were similar to those observed in the overall po...
Quantitative ultrasonography is attractive as a test for osteoporosis, being precise, radiation-f... more Quantitative ultrasonography is attractive as a test for osteoporosis, being precise, radiation-free, portable, and inexpensive, but it is still no substitute for the gold-standard test, dual-energy x-ray absorptiometry (DXA). At present, it cannot be used to diagnose osteoporosis or to monitor the effects of medications on bone density. As more data become available, however, it may play a larger role. A thorough understanding of the utility and limitations of this test is necessary for using it effectively in clinical practice.
Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when ... more Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when consistently performed in exact accordance with the manufacturer&#39;s recommendations. Precision must be quantified at each densitometry facility in precision studies of the various skeletal sites used for monitoring. The precision, as the root-mean-square standard deviation or root-mean-square coefficient of variation, is then used to determine the change in bone density that constitutes the least significant change and the minimum interval between follow-up measurements. Until precision studies are performed, the least significant change cannot be determined for any level of statistical confidence, making the interpretation of serial studies impossible.
For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest u... more For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest using the lowest bone mineral density T-score of the lumbar spine (LS), femoral neck (FN), or total hip (TH). For the LS, use of the total spine (L1-L4) T-score is suggested. Although controversial, some authors have suggested using a single lumbar vertebra of L1-L4 with the lowest T-score to diagnose osteoporosis. We compared the ability of various T-score approaches [lowest single LS vertebra of L1-L4; total spine; FN; TH; and the lowest T-score of total spine, FN, or TH to diagnose osteoporosis in 2560 postmenopausal women from the Multiple Outcomes of Raloxifene Evaluation trial placebo group. The discriminatory ability of each T-score approach to identify women with or without vertebral fracture was compared using the area under receiver-operating characteristic curve. When the lowest single LS T-score of L1-L4 and the total spine T-score were used, 77% and 57% of women were categorized as having osteoporosis, respectively. These T-score approaches had similar ability for discriminating between women with or without prevalent vertebral fractures and for predicting the risk of incident vertebral fractures. The lowest single LS vertebra T-score identified a greater proportion of women with osteoporosis than currently accepted approaches. Thus, the WHO diagnostic classification should not be applied to single vertebral T-scores. This analysis supports the current International Society for Clinical Densitometry position to use the total spine T-score for osteoporosis diagnosis.
Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in b... more Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in bone mineralization and motor function, but it is unclear whether the medication can affect fracture healing in adult HPP patients. We present the course of fracture healing in two adults with HPP on enzyme replacement. Case 1 is a 41-year-old female with infantile-onset HPP who was wheelchair-bound due to a nonhealing tibial fragility fracture sustained 3 years before and also had nonhealing femoral pseudofracture sustained 17 years before starting asfotase alfa therapy in December 2015. One month after medication initiation, she underwent elective osteotomy of tibia and fibula with intramedullary nail fixation. After 3 months of enzyme replacement, she was full weight-bearing and radiographs demonstrated callus formation at osteotomy sites, and at 11 months of therapy, radiographs showed union of the osteotomies. By 11 months of asfotase alfa therapy, there was near resolution of the fe...
On St. Paul Island, a remnant of the Bering Land Bridge, woolly mammoths persisted until 5,600 yr... more On St. Paul Island, a remnant of the Bering Land Bridge, woolly mammoths persisted until 5,600 yr BP with no known predators or competitors, providing a natural system for studying hypothesized environmental drivers of extinction. These include overheating due to rising temperatures, starvation, and drought. Here, we test these hypotheses using Niche Mapper and LPJ-GUESS to mechanistically estimate mammoth metabolic rates and dietary and freshwater requirements and, from these, estimate variations in island carrying capacity on St. Paul for the last 17,000 yr. Population carrying capacity may have been several hundred individuals at the time of initial isolation from the mainland. Adult mammoths could have fasted for two to three months, indicating a necessary ability to access snow-buried forage. During the Holocene, vegetation net primary productivity increased, but shrinking island area overrode increased net primary productivity (NPP), lowering carrying capacity to ~100 individu...
The Journal of clinical endocrinology and metabolism, Jan 9, 2016
Denosumab-induced parathyroid hormone (PTH) elevation may stimulate early bone formation. Evaluat... more Denosumab-induced parathyroid hormone (PTH) elevation may stimulate early bone formation. Evaluate whether denosumab-induced changes of intact (i)PTH result in early anabolic effects according to histomorphometry and bone turnover markers (BTM) compared with teriparatide, an established anabolic agent. This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months. United States and Canadian sites. Sixty-nine postmenopausal women with osteoporosis. Teriparatide (20 μg/day) for 6 months; denosumab (60 mg once). Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface (MS/BS); histomorphometric indices in 4 bone envelopes; BTM and iPTH at baseline, 1, 3, and 6 months. After denosumab, iPTH peaked at month 1 (P<0.001) then declined, remaining above baseline through month 6 (P≤0.01); after teriparatide, iPTH declined at all timepoints (P<0.001). From ba...
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry, Jan 29, 2015
The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researcher... more 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.
Advanced age is an important risk factor for fracture. The Abaloparatide Comparator Trial In Vert... more Advanced age is an important risk factor for fracture. The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) trial showed that subcutaneous abaloparatide increased bone mineral density (BMD) and reduced the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. This study describes the effects of abaloparatide in the subgroup of women aged 80 or more years in ACTIVE. Post hoc analyses of BMD and fracture incidence in this subgroup of women who received abaloparatide or placebo in the 18-month, phase 3, double-blind, randomized controlled ACTIVE trial. The mean ages of the women ≥80 years were 81.9 and 81.7 years in the placebo (n = 43) and abaloparatide (n = 51) groups, respectively. The increases in BMD from baseline to 18 months with abaloparatide treatment were 3.9% at the total hip (P < 0.001), 3.6% at the femoral neck (P < 0.01), and 12.1% at the lumbar spine (P < 0.001), and were similar to those observed in the overall po...
Quantitative ultrasonography is attractive as a test for osteoporosis, being precise, radiation-f... more Quantitative ultrasonography is attractive as a test for osteoporosis, being precise, radiation-free, portable, and inexpensive, but it is still no substitute for the gold-standard test, dual-energy x-ray absorptiometry (DXA). At present, it cannot be used to diagnose osteoporosis or to monitor the effects of medications on bone density. As more data become available, however, it may play a larger role. A thorough understanding of the utility and limitations of this test is necessary for using it effectively in clinical practice.
Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when ... more Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when consistently performed in exact accordance with the manufacturer&#39;s recommendations. Precision must be quantified at each densitometry facility in precision studies of the various skeletal sites used for monitoring. The precision, as the root-mean-square standard deviation or root-mean-square coefficient of variation, is then used to determine the change in bone density that constitutes the least significant change and the minimum interval between follow-up measurements. Until precision studies are performed, the least significant change cannot be determined for any level of statistical confidence, making the interpretation of serial studies impossible.
For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest u... more For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest using the lowest bone mineral density T-score of the lumbar spine (LS), femoral neck (FN), or total hip (TH). For the LS, use of the total spine (L1-L4) T-score is suggested. Although controversial, some authors have suggested using a single lumbar vertebra of L1-L4 with the lowest T-score to diagnose osteoporosis. We compared the ability of various T-score approaches [lowest single LS vertebra of L1-L4; total spine; FN; TH; and the lowest T-score of total spine, FN, or TH to diagnose osteoporosis in 2560 postmenopausal women from the Multiple Outcomes of Raloxifene Evaluation trial placebo group. The discriminatory ability of each T-score approach to identify women with or without vertebral fracture was compared using the area under receiver-operating characteristic curve. When the lowest single LS T-score of L1-L4 and the total spine T-score were used, 77% and 57% of women were categorized as having osteoporosis, respectively. These T-score approaches had similar ability for discriminating between women with or without prevalent vertebral fractures and for predicting the risk of incident vertebral fractures. The lowest single LS vertebra T-score identified a greater proportion of women with osteoporosis than currently accepted approaches. Thus, the WHO diagnostic classification should not be applied to single vertebral T-scores. This analysis supports the current International Society for Clinical Densitometry position to use the total spine T-score for osteoporosis diagnosis.
Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in b... more Infants and children with hypophosphatasia (HPP) treated with asfotase alfa show improvement in bone mineralization and motor function, but it is unclear whether the medication can affect fracture healing in adult HPP patients. We present the course of fracture healing in two adults with HPP on enzyme replacement. Case 1 is a 41-year-old female with infantile-onset HPP who was wheelchair-bound due to a nonhealing tibial fragility fracture sustained 3 years before and also had nonhealing femoral pseudofracture sustained 17 years before starting asfotase alfa therapy in December 2015. One month after medication initiation, she underwent elective osteotomy of tibia and fibula with intramedullary nail fixation. After 3 months of enzyme replacement, she was full weight-bearing and radiographs demonstrated callus formation at osteotomy sites, and at 11 months of therapy, radiographs showed union of the osteotomies. By 11 months of asfotase alfa therapy, there was near resolution of the fe...
On St. Paul Island, a remnant of the Bering Land Bridge, woolly mammoths persisted until 5,600 yr... more On St. Paul Island, a remnant of the Bering Land Bridge, woolly mammoths persisted until 5,600 yr BP with no known predators or competitors, providing a natural system for studying hypothesized environmental drivers of extinction. These include overheating due to rising temperatures, starvation, and drought. Here, we test these hypotheses using Niche Mapper and LPJ-GUESS to mechanistically estimate mammoth metabolic rates and dietary and freshwater requirements and, from these, estimate variations in island carrying capacity on St. Paul for the last 17,000 yr. Population carrying capacity may have been several hundred individuals at the time of initial isolation from the mainland. Adult mammoths could have fasted for two to three months, indicating a necessary ability to access snow-buried forage. During the Holocene, vegetation net primary productivity increased, but shrinking island area overrode increased net primary productivity (NPP), lowering carrying capacity to ~100 individu...
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