Introduction-Vitamin D deficiency is common in patients with primary hyperparathyroidism (PHPT). ... more Introduction-Vitamin D deficiency is common in patients with primary hyperparathyroidism (PHPT). The presence of low levels of vitamin D may affect the skeletal consequences of PHPT.
Bariatric surgery is an eff ective and increasingly common treatment for severe obesity and its m... more Bariatric surgery is an eff ective and increasingly common treatment for severe obesity and its many comorbidities. The side-eff ects of bariatric surgery can include detrimental eff ects on bone and mineral metabolism. Bone disease in patients who have had bariatric surgery is aff ected by preoperative abnormalities in bone and mineral metabolism related to severe obesity. Changes that arise after bariatric surgery are specifi c to procedure type: the most pronounced abnormalities in calciotropic hormones and bone loss are noted after procedures that result in the most malabsorption. The most consistent site for bone loss after all bariatric procedures is at the hip. There are limitations of dual-energy x-ray absorptiometry technology in this population, including artefact introduced by adipose tissue itself. Bone loss after bariatric surgery is probably multifactorial. Proposed mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Few data for fracture risk in the bariatric population are available, and this is a crucial area for additional research. Treatment should be geared toward correction of nutritional defi ciencies and study of bone mineral density in high-risk patients. We explore the skeletal response to bariatric surgery, potential mechanisms for changes, and strategies for management.
The objective of this study was to characterize changes in metabolic bone parameters following ba... more The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH) 2 D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH) 2 D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH) 2 D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH) 2 D levels and increased bone turnover markers.
Background-Obese adults are frequently vitamin D deficient before bariatric surgery; whether simi... more Background-Obese adults are frequently vitamin D deficient before bariatric surgery; whether similar abnormalities exist in morbidly obese adolescents is unknown.
Endocrinology and Metabolism Clinics of North America, 2007
Survival after solid-organ and bone marrow transplantation (BMT) has improved markedly during the... more Survival after solid-organ and bone marrow transplantation (BMT) has improved markedly during the past 2 decades, mainly because of the addition of calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus, to posttransplantation immunosuppressive regimens. With improved survival has come a greater appreciation of complications such as osteoporosis and vertebral fractures that adversely influence patients' quality of life. Osteoporosis after transplantation is related both to pretransplantation factors and to early, rapid posttransplantation bone loss, probably caused by the concomitant administration of high-dose glucocorticoids (GCs) and calcineurin inhibitors. This article discusses the factors that contribute to low bone mass in candidates for transplantation and transplant recipients and the studies that have assessed various treatment strategies for prevention and treatment of transplantation osteoporosis. The reader also is referred to several recent reviews and articles on this topic [1-5] that contain detailed references.
Endocrinology and Metabolism Clinics of North America, 2003
Either your web browser doesn&#x27;t support Javascript or it is currently turned off. In the... more Either your web browser doesn&#x27;t support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. ... Find all citations by this author (default). ... Find all citations by this author (default).
By conventional 2-dimensional histomorphometric analysis, we have shown that cancellous bone arch... more By conventional 2-dimensional histomorphometric analysis, we have shown that cancellous bone architecture is markedly altered in hypoparathyroidism. We have now extended these observations to a 3-dimensional analysis using microcomputed tomography. Percutaneous iliac crest bone biopsies were analyzed by high-resolution microcomputed tomography from the following 25 subjects with hypoparathyroidism: 5 postmenopausal women, 13 premenopausal women and 7 men. Thirteen living premenopausal healthy controls and 12 cadaver subjects without bone disease served as matched controls. Hypoparathyroid subjects had significantly greater bone surface density (BS/TV: 5.74 ± 4.7 vs. 3.73 ± 1.01 mm 2 /mm 3 [mean ± SD]; p=0.04), trabecular thickness (Tb.Th: 0.25 ± 0.19 vs. 0.17 ± 0.04 mm; p=0.04), trabecular number (Tb.N: 2.99 ± 3.4 vs. 1.62 ± 0.39 mm −1 ; p=0.05) and connectivity density (Conn.D: 16.63 ± 18.7 vs. 8.39 ± 5.8 mm 3 ; p=0.04) in comparison to matched controls. When an additional 8 hypoparathyorid (total n= 33) and 24 cadaver (total cadaver n= 36) subjects were added to the groups for an unmatched analysis, hypoparathyroid subjects had significantly greater cancellous bone volume (BV/TV: 26.98 ± 10 vs. 15.39 ± 4%; p< 0.001), , while trabecular separation (Tb.Sp: 0.642 ± 0.10 vs. 0.781 ± 0.13 mm; p<0.001) and estimation of the platerod characteristic (SMI: −0.457 ± 1.52 vs. 0.742 ± 0.51; p<0.001) were significantly lower, the latter observation implying a more plate-like trabecular structure. Variables of cancellous bone structure in the hypoparathyroid subjects, as assessed by microcomputed tomography, were highly correlated with those assessed by conventional histomorphometry. We conclude that cancellous bone in hypoparathyroidism is abnormal, suggesting that parathyroid hormone is required to maintain normal trabecular structure. The effect of these structural changes on bone strength remains to be determined.
The introduction of cyclosporine to transplantation immunology in the early 1980s resulted in mar... more The introduction of cyclosporine to transplantation immunology in the early 1980s resulted in marked improvement in short-term graft and patient survival and ushered in a new era for patients with end-stage renal, hepatic, cardiac, pulmonary, and hematopoietic disease. The addition of cyclosporine, and later tacrolimus, to post-transplantation immunosuppression regimens permitted the use of lower doses of glucocorticoids (GCs). Therefore, it was initially expected that glucocorticoid-induced osteoporosis would be less of a problem in the cyclosporine era. During the past two decades, however, it has become clear that organ transplant recipients managed with cyclosporine and probably tacrolimus sustain rapid bone loss and fragility fractures (1–4). Moreover, transplantation-related bone loss and fractures may become increasingly prevalent as more patients continue to undergo organ transplantation each year and survival continues to improve (5). This review will summarize our current understanding of the effects of the most commonly prescribed immunosuppressive agents on bone and mineral metabolism. The epidemiology, natural history, and pathogenesis of bone loss and fracture after various types of organ transplantation will be reviewed. Recommendations for prevention of the acute phase of bone loss after organ transplantation, and treatment of established osteoporosis in organ transplantation candidates and recipients will be summarized
The objectives of this study were to evaluate the capability of a novel ultrasound device to clin... more The objectives of this study were to evaluate the capability of a novel ultrasound device to clinically estimate bone mineral density (BMD) at the 1/3 radius. The device rests on a desktop and is portable, and permits real-time evaluation of the radial BMD. The device measures two net time delay (NTD) parameters, NTD(DW) and NTD(CW). NTD(DW) is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue, cortex and medullary cavity, and the transit time through soft tissue only of equal overall distance. NTD(CW) is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue and cortex only, and the transit time through soft tissue only again of equal overall distance. The square root of the product of these two parameters is a measure of the radial BMD at the 1/3 location as measured by dual-energy X-ray absorptiometry (DXA). A clinical IRB-approved study measured ultrasonically 60 adults at the 1/3 radius. BMD was also measured at the same anatomic site and time using DXA. A linear regression using NTD produced a linear correlation coefficient of 0.93 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). These results are consistent with previously reported simulation and in vitro studies. In conclusion, although X-ray methods are effective in bone mass assessment, osteoporosis remains one of the largest undiagnosed and under-diagnosed diseases in the world today. The research described here should enable significant expansion of diagnosis and monitoring of osteoporosis through a desktop device that ultrasonically assesses bone mass at the 1/3 radius.
Lenalidomide, a recently developed immunomodulatory drug, shares the antiangiogenic and antitumor... more Lenalidomide, a recently developed immunomodulatory drug, shares the antiangiogenic and antitumor properties of thalidomide. While there is a known association between thalidomide and hypothyroidism, to our knowledge, there have been no prior reports of thyrotoxicosis associated with thalidomide or lenalidomide treatment. Herein, we report the case of a patient who developed transient thyrotoxicosis while receiving lenalidomide in a clinical trial for metastatic renal cell carcinoma. The time course and biochemical features of this patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s presentation are most consistent with immune-mediated subacute destructive thyroiditis. This case highlights the importance of monitoring thyroid function in the growing number of patients being treated with lenalidomide.
The objective of this study was to characterize changes in metabolic bone parameters following ba... more The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH) 2 D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH) 2 D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH) 2 D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH) 2 D levels and increased bone turnover markers.
Myxococcus xanthus has a complex life cycle that involves vegetative growth and development. Prev... more Myxococcus xanthus has a complex life cycle that involves vegetative growth and development. Previously, we described the espAB locus that is involved in timing events during the initial stages of fruiting body formation. Deletion of espA caused early aggregation and sporulation, whereas deletion of espB caused delayed aggregation and sporulation resulting in reduced spore yields. In this study, we describe two genes, pktA5 and pktB8, that flank the espAB locus and encode Ser/Thr protein kinase (STPK) homologues. Cells deficient in pktA5 or pktB8 formed translucent mounds and produced low spore yields, similar in many respects to espB mutants. Double mutant analysis revealed that espA was epistatic to pktA5 and pktB8 with respect to aggregation and fruiting body morphology, but that pktA5 and pktB8 were epistatic to espA with respect to sporulation efficiency. Expression profiles of pktA5-lacZ and pktB8-lacZ fusions and Western blot analysis showed that the STPKs are expressed under vegetative and developmental conditions. In vitro kinase assays demonstrated that the RD kinase, PktA5, autophosphorylated on threonine residue(s) and phosphorylated the artificial substrate, myelin basic protein. In contrast, autophosphorylation of the non-RD kinase, PktB8, was not observed in vitro; however, the phenotype of a pktB8 kinase-dead point mutant resembled the pktB8 deletion mutant, indicating that this residue was important for function and that it likely functions as a kinase in vivo. Immuno-precipitation of Tap-tagged PktA5 and PktB8 revealed an interaction with EspA during development in M. xanthus. These results, taken together, suggest that PktA5 and PktB8 are STPKs that function during development by interacting with EspA and EspB to regulate M. xanthus development.
Introduction-Vitamin D deficiency is common in patients with primary hyperparathyroidism (PHPT). ... more Introduction-Vitamin D deficiency is common in patients with primary hyperparathyroidism (PHPT). The presence of low levels of vitamin D may affect the skeletal consequences of PHPT.
Bariatric surgery is an eff ective and increasingly common treatment for severe obesity and its m... more Bariatric surgery is an eff ective and increasingly common treatment for severe obesity and its many comorbidities. The side-eff ects of bariatric surgery can include detrimental eff ects on bone and mineral metabolism. Bone disease in patients who have had bariatric surgery is aff ected by preoperative abnormalities in bone and mineral metabolism related to severe obesity. Changes that arise after bariatric surgery are specifi c to procedure type: the most pronounced abnormalities in calciotropic hormones and bone loss are noted after procedures that result in the most malabsorption. The most consistent site for bone loss after all bariatric procedures is at the hip. There are limitations of dual-energy x-ray absorptiometry technology in this population, including artefact introduced by adipose tissue itself. Bone loss after bariatric surgery is probably multifactorial. Proposed mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Few data for fracture risk in the bariatric population are available, and this is a crucial area for additional research. Treatment should be geared toward correction of nutritional defi ciencies and study of bone mineral density in high-risk patients. We explore the skeletal response to bariatric surgery, potential mechanisms for changes, and strategies for management.
The objective of this study was to characterize changes in metabolic bone parameters following ba... more The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH) 2 D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH) 2 D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH) 2 D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH) 2 D levels and increased bone turnover markers.
Background-Obese adults are frequently vitamin D deficient before bariatric surgery; whether simi... more Background-Obese adults are frequently vitamin D deficient before bariatric surgery; whether similar abnormalities exist in morbidly obese adolescents is unknown.
Endocrinology and Metabolism Clinics of North America, 2007
Survival after solid-organ and bone marrow transplantation (BMT) has improved markedly during the... more Survival after solid-organ and bone marrow transplantation (BMT) has improved markedly during the past 2 decades, mainly because of the addition of calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus, to posttransplantation immunosuppressive regimens. With improved survival has come a greater appreciation of complications such as osteoporosis and vertebral fractures that adversely influence patients' quality of life. Osteoporosis after transplantation is related both to pretransplantation factors and to early, rapid posttransplantation bone loss, probably caused by the concomitant administration of high-dose glucocorticoids (GCs) and calcineurin inhibitors. This article discusses the factors that contribute to low bone mass in candidates for transplantation and transplant recipients and the studies that have assessed various treatment strategies for prevention and treatment of transplantation osteoporosis. The reader also is referred to several recent reviews and articles on this topic [1-5] that contain detailed references.
Endocrinology and Metabolism Clinics of North America, 2003
Either your web browser doesn&#x27;t support Javascript or it is currently turned off. In the... more Either your web browser doesn&#x27;t support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. ... Find all citations by this author (default). ... Find all citations by this author (default).
By conventional 2-dimensional histomorphometric analysis, we have shown that cancellous bone arch... more By conventional 2-dimensional histomorphometric analysis, we have shown that cancellous bone architecture is markedly altered in hypoparathyroidism. We have now extended these observations to a 3-dimensional analysis using microcomputed tomography. Percutaneous iliac crest bone biopsies were analyzed by high-resolution microcomputed tomography from the following 25 subjects with hypoparathyroidism: 5 postmenopausal women, 13 premenopausal women and 7 men. Thirteen living premenopausal healthy controls and 12 cadaver subjects without bone disease served as matched controls. Hypoparathyroid subjects had significantly greater bone surface density (BS/TV: 5.74 ± 4.7 vs. 3.73 ± 1.01 mm 2 /mm 3 [mean ± SD]; p=0.04), trabecular thickness (Tb.Th: 0.25 ± 0.19 vs. 0.17 ± 0.04 mm; p=0.04), trabecular number (Tb.N: 2.99 ± 3.4 vs. 1.62 ± 0.39 mm −1 ; p=0.05) and connectivity density (Conn.D: 16.63 ± 18.7 vs. 8.39 ± 5.8 mm 3 ; p=0.04) in comparison to matched controls. When an additional 8 hypoparathyorid (total n= 33) and 24 cadaver (total cadaver n= 36) subjects were added to the groups for an unmatched analysis, hypoparathyroid subjects had significantly greater cancellous bone volume (BV/TV: 26.98 ± 10 vs. 15.39 ± 4%; p< 0.001), , while trabecular separation (Tb.Sp: 0.642 ± 0.10 vs. 0.781 ± 0.13 mm; p<0.001) and estimation of the platerod characteristic (SMI: −0.457 ± 1.52 vs. 0.742 ± 0.51; p<0.001) were significantly lower, the latter observation implying a more plate-like trabecular structure. Variables of cancellous bone structure in the hypoparathyroid subjects, as assessed by microcomputed tomography, were highly correlated with those assessed by conventional histomorphometry. We conclude that cancellous bone in hypoparathyroidism is abnormal, suggesting that parathyroid hormone is required to maintain normal trabecular structure. The effect of these structural changes on bone strength remains to be determined.
The introduction of cyclosporine to transplantation immunology in the early 1980s resulted in mar... more The introduction of cyclosporine to transplantation immunology in the early 1980s resulted in marked improvement in short-term graft and patient survival and ushered in a new era for patients with end-stage renal, hepatic, cardiac, pulmonary, and hematopoietic disease. The addition of cyclosporine, and later tacrolimus, to post-transplantation immunosuppression regimens permitted the use of lower doses of glucocorticoids (GCs). Therefore, it was initially expected that glucocorticoid-induced osteoporosis would be less of a problem in the cyclosporine era. During the past two decades, however, it has become clear that organ transplant recipients managed with cyclosporine and probably tacrolimus sustain rapid bone loss and fragility fractures (1–4). Moreover, transplantation-related bone loss and fractures may become increasingly prevalent as more patients continue to undergo organ transplantation each year and survival continues to improve (5). This review will summarize our current understanding of the effects of the most commonly prescribed immunosuppressive agents on bone and mineral metabolism. The epidemiology, natural history, and pathogenesis of bone loss and fracture after various types of organ transplantation will be reviewed. Recommendations for prevention of the acute phase of bone loss after organ transplantation, and treatment of established osteoporosis in organ transplantation candidates and recipients will be summarized
The objectives of this study were to evaluate the capability of a novel ultrasound device to clin... more The objectives of this study were to evaluate the capability of a novel ultrasound device to clinically estimate bone mineral density (BMD) at the 1/3 radius. The device rests on a desktop and is portable, and permits real-time evaluation of the radial BMD. The device measures two net time delay (NTD) parameters, NTD(DW) and NTD(CW). NTD(DW) is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue, cortex and medullary cavity, and the transit time through soft tissue only of equal overall distance. NTD(CW) is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue and cortex only, and the transit time through soft tissue only again of equal overall distance. The square root of the product of these two parameters is a measure of the radial BMD at the 1/3 location as measured by dual-energy X-ray absorptiometry (DXA). A clinical IRB-approved study measured ultrasonically 60 adults at the 1/3 radius. BMD was also measured at the same anatomic site and time using DXA. A linear regression using NTD produced a linear correlation coefficient of 0.93 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). These results are consistent with previously reported simulation and in vitro studies. In conclusion, although X-ray methods are effective in bone mass assessment, osteoporosis remains one of the largest undiagnosed and under-diagnosed diseases in the world today. The research described here should enable significant expansion of diagnosis and monitoring of osteoporosis through a desktop device that ultrasonically assesses bone mass at the 1/3 radius.
Lenalidomide, a recently developed immunomodulatory drug, shares the antiangiogenic and antitumor... more Lenalidomide, a recently developed immunomodulatory drug, shares the antiangiogenic and antitumor properties of thalidomide. While there is a known association between thalidomide and hypothyroidism, to our knowledge, there have been no prior reports of thyrotoxicosis associated with thalidomide or lenalidomide treatment. Herein, we report the case of a patient who developed transient thyrotoxicosis while receiving lenalidomide in a clinical trial for metastatic renal cell carcinoma. The time course and biochemical features of this patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s presentation are most consistent with immune-mediated subacute destructive thyroiditis. This case highlights the importance of monitoring thyroid function in the growing number of patients being treated with lenalidomide.
The objective of this study was to characterize changes in metabolic bone parameters following ba... more The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH) 2 D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH) 2 D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH) 2 D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH) 2 D levels and increased bone turnover markers.
Myxococcus xanthus has a complex life cycle that involves vegetative growth and development. Prev... more Myxococcus xanthus has a complex life cycle that involves vegetative growth and development. Previously, we described the espAB locus that is involved in timing events during the initial stages of fruiting body formation. Deletion of espA caused early aggregation and sporulation, whereas deletion of espB caused delayed aggregation and sporulation resulting in reduced spore yields. In this study, we describe two genes, pktA5 and pktB8, that flank the espAB locus and encode Ser/Thr protein kinase (STPK) homologues. Cells deficient in pktA5 or pktB8 formed translucent mounds and produced low spore yields, similar in many respects to espB mutants. Double mutant analysis revealed that espA was epistatic to pktA5 and pktB8 with respect to aggregation and fruiting body morphology, but that pktA5 and pktB8 were epistatic to espA with respect to sporulation efficiency. Expression profiles of pktA5-lacZ and pktB8-lacZ fusions and Western blot analysis showed that the STPKs are expressed under vegetative and developmental conditions. In vitro kinase assays demonstrated that the RD kinase, PktA5, autophosphorylated on threonine residue(s) and phosphorylated the artificial substrate, myelin basic protein. In contrast, autophosphorylation of the non-RD kinase, PktB8, was not observed in vitro; however, the phenotype of a pktB8 kinase-dead point mutant resembled the pktB8 deletion mutant, indicating that this residue was important for function and that it likely functions as a kinase in vivo. Immuno-precipitation of Tap-tagged PktA5 and PktB8 revealed an interaction with EspA during development in M. xanthus. These results, taken together, suggest that PktA5 and PktB8 are STPKs that function during development by interacting with EspA and EspB to regulate M. xanthus development.
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