Montreal 2008Montreal 2008
Effects of bone on fatEffects of bone on fat
massmass
Highlights ASBMR, part 2Highlights ASBMR,...
ASBMR
Effects ofEffects of fat massfat mass onon bonebone
 Fat mass imposes mechanical stress on boneFat mass imposes mec...
ASBMR
Osteoblasts andOsteoblasts and
adipocytes originateadipocytes originate
from commonfrom common
progenitor-progenitor...
ASBMR
Effects ofEffects of bonebone onon fatfat massmass
Hormones that regulate fat/glucose metabolism have
effects on the...
ASBMR
Effects ofEffects of bonebone onon fat massfat mass
 SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity Sp...
ASBMR
OsteocalcinOsteocalcin
Protein of 49 amino acidsProtein of 49 amino acids
3 glutamin residues3 glutamin residues
Aft...
ASBMR
VITAMIN K CYCLEVITAMIN K CYCLE..
ORAL ANTICOAGULANTS INHIBIT THE
RECYCLING OF VITAMIN K
‘Inactive’
OSTEOCALCIN
OSTEO...
ASBMR
Seeman et al. NEJM 2006
Bone turnoverBone turnover
PINP
BALP
Osteocalcine
CTx
Crosslinks
TRAP
ASBMR
Effects ofEffects of bonebone onon fat massfat mass
 SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity Sp...
ASBMR
Background:
In obese patients with diabetes, gastric bypass
surgery (GBS) through unknown mechanisms, leads
to ~90% ...
ASBMR
Study is designed to determine:
1) uOC levels in obese patients with and without diabetes
2) the effect of Gastric B...
ASBMR
40 obese patients (BMI: 48.5±9.7 kg/m2)
- 19 had type 2 diabetes,
- 12 patients that had GBS 12-24 months prior to t...
ASBMR
SA 444SA 444
Osteocalcin andOsteocalcin and
ObesityObesity
SpagnoliSpagnoli
ASBMR
Inverse correlation was found between:
uOC and HMW-adiponectin r = -0.28 p=0.02
uOC and HOMA r = -0.33 p=0.006
HMW-a...
ASBMR
Effects ofEffects of bonebone onon fat massfat mass
 SA 444 Osteocalcin and Obesity Spagnoli
Obese and Post Gastric...
ASBMR
SU 461 Osteocalcin and type II Diabetes
Nguyen
Background:
 Serum osteocalcin (OC), a 49-amino acid bone matrix pro...
ASBMR
Serum OC, sex hormone binding globulin (SHBG), 25(OH)D, and PTH were
measured by radioimmunoassay in 443 men aged 60...
ASBMR
ASBMR
ASBMR
ASBMR
SU 461 Osteocalcin and type II Diabetes
Nguyen
Conclusion
 Osteocalcin and serum testosteron were independent
risk ...
ASBMR
Effects ofEffects of bonebone onon fat massfat mass
 SA 444 Osteocalcin and Obesity Spagnoli
Obese and Post Gastric...
ASBMR
Background:
 Osteocalcin affect adiposity and glucose homeostasis in
mice, suggesting that the skeleton via an endo...
ASBMR
SU 459 Osteocalcin and Fat Mass /Glucose
Kindblom
Methods:Methods:
1010 elderly men (75.3± 3.2 years) of the MrOS Sw...
ASBMR
SU 459 Osteocalcin and Fat Mass /Glucose
Kindblom
BMI
Total
body fat
Glucose
(fasting)
ASBMR
Pearson’s correlation coefficients for
associations with Osteocalcin
ASBMR
ASBMR
SU 459 Osteocalcin and Fat Mass /Glucose
Kindblom
ASBMR
ASBMR
SU 459 Osteocalcin and Fat Mass /Glucose
Kindblom
 PINPPINP is strongly associated withis strongly associated with ...
ASBMR
SU 459 Osteocalcin and Fat Mass /Glucose
Kindblom
Conclusion:Conclusion:
 Osteocalcin is a negative predictor of fa...
ASBMR
Effects ofEffects of bonebone onon fat massfat mass
 SA 444 Osteocalcin and Obesity Spagnoli
Obese and Post Gastric...
ASBMR
SU 225 Osteocalcin gene and Body Fat Mass
McGuigan
Aim:
 To determine the relationship between variation in the
ost...
ASBMR
SU 225 Osteocalcin gene and Body Fat Mass
McGuigan
4 SNPs around Osteocalcin locus on Chr 1,
including rs1800247 loc...
ASBMR
SU 225 Osteocalcin gene and Body Fat Mass
McGuigan
• Osteocalcin SNP’s were associated with % total body fat at base...
ASBMR
SU 225 Osteocalcin gene and Body Fat Mass
McGuigan
Conclusion:
 The variation in the osteocalcin gene is linked bot...
ASBMR
Effects ofEffects of bonebone onon fat massfat mass
 SA 444 Osteocalcin and Obesity Spagnoli
Obese and Post Gastric...
ASBMR
SA 198 Osteocalcin and Carotid Plaques / Metabolic
Syndrome Waern
Aim:
To investigate the relationship between
osteo...
ASBMR
Results
• Osteocalcin increased by 44 percent from 70 to 86 years of age.
This increase was related to, but independ...
ASBMR
OC was inversely related to the risk of having bilateral carotoid plaques
(OR per SD increase in osteocalcin 0.68 (9...
ASBMR
Conclusion:
Low serum osteocalcin predicts high glucose and carotid
plaques and indicators of the metabolic syndrome...
ASBMR
bone regulates the
energy homeostasis
ASBMR 2008
osteocalcin
ASBMR
Central Regulation of BoneCentral Regulation of Bone
RemodelingRemodeling
interaction between bone and braininteract...
ASBMR
Met dank aan de Nederlandse collegae voor de leerzame discussies tijdens
de ASBMR
ASBMR
ASBMR
 Diabetic subjects had lower plasma osteocalcin (-21.7 %, p< 0.001)Diabetic subjects had lower plasma osteocalcin (...
ASBMR
Methods and population
619 randomly selected 70 years old men and women
longitudinal study with examinations at age ...
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Seminar 08-10-2008 - effects of bone on fat mass

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  • Common factors shared in osteoblast and adipocyte differentiation. Osteoblasts and adipocytes originate from common progenitor-mesenchymal stem cells. The balance of their differentiation is determined by several common factors, such as PPAR-γ, Wnt, TGF-β, leptin, and estrogen. Adipocytes express and secrete a variety of bioactive peptides, such as estrogen, resistin, leptin, adiponectin, and inflammatory cytokines. Some of these peptides affect human energy homeostasis and may be involved in bone metabolism. Adapted from Reference 15. It was previously believed that obesity and osteoporosis were two unrelated diseases, but recent studies have shown that both diseases share several common genetic and environmental factors. Body fat mass, a component of body weight, is one of the most important indices of obesity, and a substantial body of evidence indicates that fat mass may have beneficial effects on bone. Contrasting studies, however, suggest that excessive fat mass may not protect against osteoporosis or osteoporotic fracture. Differences in experimental design, sample structure, and even the selection of covariates may account for some of these inconsistent or contradictory results. Despite the lack of a clear consensus regarding the impact of effects of fat on bone, a number of mechanistic explanations have been proposed to support the observed epidemiologic and physiologic associations between fat and bone. The common precursor stem cell that leads to the differentiation of both adipocytes and osteoblasts, as well the secretion of adipocyte-derived hormones that affect bone development, may partially explain these associations. Based on our current state of knowledge, it is unclear whether fat has beneficial effects on bone. We anticipate that this will be an active and fruitful focus of research in the coming years.
  • Dr. E. van der Veer The Remodeling Cycle on a Trabecula. A microcrack severs canaliculi, which causes osteocytic apoptosis, with the location and extent of the damage defined by signals to lining cells. Lining cells and osteocytes release local factors that attract cells from blood and marrow into the remodeling compartment in which osteoclastogenesis occurs. Osteoclasts resorb matrix and the microcrack, then successive teams of osteoblasts deposit new lamellar bone. Osteoblasts that are trapped in the matrix become osteocytes; others die or form new, flattened osteoblast lining cells.
  • Cystatin C = kidney function
  • Common factors shared in osteoblast and adipocyte differentiation. Osteoblasts and adipocytes originate from common progenitor-mesenchymal stem cells. The balance of their differentiation is determined by several common factors, such as PPAR-γ, Wnt, TGF-β, leptin, and estrogen. Adipocytes express and secrete a variety of bioactive peptides, such as estrogen, resistin, leptin, adiponectin, and inflammatory cytokines. Some of these peptides affect human energy homeostasis and may be involved in bone metabolism. Adapted from Reference 15. It was previously believed that obesity and osteoporosis were two unrelated diseases, but recent studies have shown that both diseases share several common genetic and environmental factors. Body fat mass, a component of body weight, is one of the most important indices of obesity, and a substantial body of evidence indicates that fat mass may have beneficial effects on bone. Contrasting studies, however, suggest that excessive fat mass may not protect against osteoporosis or osteoporotic fracture. Differences in experimental design, sample structure, and even the selection of covariates may account for some of these inconsistent or contradictory results. Despite the lack of a clear consensus regarding the impact of effects of fat on bone, a number of mechanistic explanations have been proposed to support the observed epidemiologic and physiologic associations between fat and bone. The common precursor stem cell that leads to the differentiation of both adipocytes and osteoblasts, as well the secretion of adipocyte-derived hormones that affect bone development, may partially explain these associations. Based on our current state of knowledge, it is unclear whether fat has beneficial effects on bone. We anticipate that this will be an active and fruitful focus of research in the coming years.
  • Central regulation of bone remodeling occurs through the hypothalamus but is determined by both afferent and efferent signaling. Phase 1 is the afferent leptin signal that originates from peripheral adipocytes. Phase 2 involves the processing of this signal in the hypothalamus, which occurs in the ventromedial hypothalamus (VMH). The mediators of this phase likely include neuropeptide Y (NPY) and neuromedin U (NMU). Phase 3 represents the efferent (sympathetic) output from the hypothalamus to the β2-adrenergic receptor (β2-AR) on osteoblasts and the resultant change in transcription factors and clock genes that affect osteoblastogenesis. Suppression of osteoclastogenesis can occur indirectly through the suppression of receptor activator of NF-κB ligand (RANKL) in osteoblasts by cocaine- and amphetamine-regulated transcript (CART). NMU may mediate its effects downstream of β2-AR on the clock genes. Phase 4 represents skeletal regulation of adipocytes, most likely through the systemic release of osteocalcin. The dotted line in phase 4 represents the theoretical possibility that adipocytes could regulate osteoblast proliferation and differentiation. Other abbreviations: Y1, NPY receptor 1; Y2, NPY receptor 2; NMUR, neuromedin U receptor 2; OB, osteoblast; OC, osteoclast.
  • Seminar 08-10-2008 - effects of bone on fat mass

    1. 1. Montreal 2008Montreal 2008 Effects of bone on fatEffects of bone on fat massmass Highlights ASBMR, part 2Highlights ASBMR, part 2 Dr. E. van der VeerDr. E. van der Veer University Medical Center GroningenUniversity Medical Center Groningen Utrecht, Oct 8Utrecht, Oct 8THTH 20082008 ASBMRASBMR
    2. 2. ASBMR Effects ofEffects of fat massfat mass onon bonebone  Fat mass imposes mechanical stress on boneFat mass imposes mechanical stress on bone  Adipocytes secretes biologically active moleculesAdipocytes secretes biologically active molecules  EstrogenEstrogen  ResistinResistin  LeptinLeptin  AdiponectinAdiponectin  Interleukin – 6 (IL-6)Interleukin – 6 (IL-6)  Pancreas secretes bone-active hormonesPancreas secretes bone-active hormones  InsulinInsulin  AmylinAmylin  PreptinPreptin  Adipocytes and osteoblasts have common progenitor,Adipocytes and osteoblasts have common progenitor, the pluripotent mesenchymal stem cellthe pluripotent mesenchymal stem cell
    3. 3. ASBMR Osteoblasts andOsteoblasts and adipocytes originateadipocytes originate from commonfrom common progenitor-progenitor- mesenchymal stemmesenchymal stem cellscells Rosen et al 2006 Zhao et al 2008
    4. 4. ASBMR Effects ofEffects of bonebone onon fatfat massmass Hormones that regulate fat/glucose metabolism have effects on the skeleton, But does bone regulate the energy homeostasis? Mice with increased levels of uncarboxylated osteocalcin (uOC) are protected from type 2 diabetes regulating adiponectin secretion, Mice lacking osteocalcin display decreased B-cell proliferation, glucose intolerance and insulin resistance (Lee NG et al, Cell 2007,130:458).
    5. 5. ASBMR Effects ofEffects of bonebone onon fat massfat mass  SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity SpagnoliSpagnoli Obese and Post Gastric By-pass patientsObese and Post Gastric By-pass patients  SU 461SU 461 Osteocalcin and type II DiabetesOsteocalcin and type II Diabetes NguyenNguyen Men aged 60+  SU 459SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Elderly Swedish Men  SU 225SU 225 Osteocalcin gene andOsteocalcin gene and Body Fat MassBody Fat Mass McGuiganMcGuigan Elderly Swedish WomenElderly Swedish Women  SA 198SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern
    6. 6. ASBMR OsteocalcinOsteocalcin Protein of 49 amino acidsProtein of 49 amino acids 3 glutamin residues3 glutamin residues After carboxylation of theAfter carboxylation of the GLU-residues binding to hydroxyapatiteGLU-residues binding to hydroxyapatite
    7. 7. ASBMR VITAMIN K CYCLEVITAMIN K CYCLE.. ORAL ANTICOAGULANTS INHIBIT THE RECYCLING OF VITAMIN K ‘Inactive’ OSTEOCALCIN OSTEOCALCIN
    8. 8. ASBMR Seeman et al. NEJM 2006 Bone turnoverBone turnover PINP BALP Osteocalcine CTx Crosslinks TRAP
    9. 9. ASBMR Effects ofEffects of bonebone onon fat massfat mass  SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity SpagnoliSpagnoli Obese and Post Gastric By-pass patientsObese and Post Gastric By-pass patients  SU 461SU 461 Osteocalcin and type II DiabetesOsteocalcin and type II Diabetes NguyenNguyen Men aged 60+  SU 459SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Elderly Swedish Men  SU 225SU 225 Osteocalcin gene andOsteocalcin gene and Body Fat MassBody Fat Mass McGuiganMcGuigan Elderly Swedish WomenElderly Swedish Women  SA 198SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern
    10. 10. ASBMR Background: In obese patients with diabetes, gastric bypass surgery (GBS) through unknown mechanisms, leads to ~90% resolution of type 2 diabetes before any significant weight loss occurs. SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity SpagnoliSpagnoli
    11. 11. ASBMR Study is designed to determine: 1) uOC levels in obese patients with and without diabetes 2) the effect of Gastric By-pass Surgery on uOC 3) the relationship of uOC with adiponectin and in turn with insulin sensitivity. SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity SpagnoliSpagnoli
    12. 12. ASBMR 40 obese patients (BMI: 48.5±9.7 kg/m2) - 19 had type 2 diabetes, - 12 patients that had GBS 12-24 months prior to the study (post-GBS) (BMI: 29±7 kg/m2); - 16 normal weight age-matched control subjects (BMI: 25±3.3 kg/m2). Measured: glucose and insulin to determine HOMA, (Homeostatic model assessment for quantifying insulin resistance) serum total and uncarboxylated osteocalcin, serum HMW-adiponectin by RIA or IRMA. SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity SpagnoliSpagnoli
    13. 13. ASBMR SA 444SA 444 Osteocalcin andOsteocalcin and ObesityObesity SpagnoliSpagnoli
    14. 14. ASBMR Inverse correlation was found between: uOC and HMW-adiponectin r = -0.28 p=0.02 uOC and HOMA r = -0.33 p=0.006 HMW-adiponectin and HOMA r = -0.32 p=0.008 Conclusion In obese patients uOC levels are decreased, and normalize post-GBS. These data support the hypothesis that uOC is a bone hormone that regulates insulin sensitivity by modulating adiponectin. Spagnoli et al postulate that normalization of uOC is a mechanism for diabetes resolution post-GBS. SA 444SA 444 Osteocalcin and ObesityOsteocalcin and Obesity SpagnoliSpagnoli
    15. 15. ASBMR Effects ofEffects of bonebone onon fat massfat mass  SA 444 Osteocalcin and Obesity Spagnoli Obese and Post Gastric By-pass patients  SU 461 Osteocalcin and type II Diabetes Nguyen Men aged 60+  SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Elderly Swedish Men  SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern  SU 225 Osteocalcin gene and Body Fat Mass McGuigan Elderly Women
    16. 16. ASBMR SU 461 Osteocalcin and type II Diabetes Nguyen Background:  Serum osteocalcin (OC), a 49-amino acid bone matrix protein, has recently been shown to be associated with diabetes in mice.  However, it is unknown whether the association is present in men. Aim:  Therefore, this study sought to examine the contribution of OC to the susceptibility of type II diabetes in men
    17. 17. ASBMR Serum OC, sex hormone binding globulin (SHBG), 25(OH)D, and PTH were measured by radioimmunoassay in 443 men aged 60+ at baseline (1989) in the Dubbo Osteoporosis Epidemiology Study. The men’s health status, including fracture and diabetes, had been monitored between 1989 and 2007. Bone mineral density (BMD), clinical risk factors, and lifestyle factors had also been obtained at baseline and subsequent biannual visits.
    18. 18. ASBMR
    19. 19. ASBMR
    20. 20. ASBMR
    21. 21. ASBMR SU 461 Osteocalcin and type II Diabetes Nguyen Conclusion  Osteocalcin and serum testosteron were independent risk factors for type II diabetes  Thus, these data suggest that lower osteocalcin were associated with an increased risk of type II diabetes in men.  The use of serum OC may help improve the prognostic accuracy of type II diabetes in men.
    22. 22. ASBMR Effects ofEffects of bonebone onon fat massfat mass  SA 444 Osteocalcin and Obesity Spagnoli Obese and Post Gastric By-pass patients  SU 461 Osteocalcin and type II Diabetes Nguyen  SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Elderly Swedish Men  SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern  SU 225 Osteocalcin gene and Body Fat Mass McGuigan Elderly Women
    23. 23. ASBMR Background:  Osteocalcin affect adiposity and glucose homeostasis in mice, suggesting that the skeleton via an endocrine mechanism influences energy metabolism. Aim:  To investigate the relationship between plasma osteocalcin and parameters reflecting fat mass and glucose homeostasis in humans. SU 459 Osteocalcin and Fat Mass /Glucose Kindblom
    24. 24. ASBMR SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Methods:Methods: 1010 elderly men (75.3± 3.2 years) of the MrOS Sweden study,1010 elderly men (75.3± 3.2 years) of the MrOS Sweden study, non-diabetic n= 857non-diabetic n= 857 diabetic n= 153.diabetic n= 153.  Fasting levels were analysed ofFasting levels were analysed of plasma osteocalcin,plasma osteocalcin, plasma glucose,plasma glucose, serum insulin andserum insulin and lipidslipids  Fat mass and lean mass were analysed using dual energy X-rayFat mass and lean mass were analysed using dual energy X-ray absorptiometry.absorptiometry.
    25. 25. ASBMR SU 459 Osteocalcin and Fat Mass /Glucose Kindblom BMI Total body fat Glucose (fasting)
    26. 26. ASBMR Pearson’s correlation coefficients for associations with Osteocalcin ASBMR
    27. 27. ASBMR SU 459 Osteocalcin and Fat Mass /Glucose Kindblom ASBMR
    28. 28. ASBMR SU 459 Osteocalcin and Fat Mass /Glucose Kindblom  PINPPINP is strongly associated withis strongly associated with OsteocalcinOsteocalcin Pearson’s r = 0.66Pearson’s r = 0.66  Both bone formation markers were included together asBoth bone formation markers were included together as covariates in linear regression models:covariates in linear regression models: OC was independently predicting glucose and fat mass,OC was independently predicting glucose and fat mass, but PINP not.but PINP not. ASBMR
    29. 29. ASBMR SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Conclusion:Conclusion:  Osteocalcin is a negative predictor of fat mass andOsteocalcin is a negative predictor of fat mass and plasma glucose in elderly menplasma glucose in elderly men  In contrast, PINP is not an independent predictorIn contrast, PINP is not an independent predictor  These human data support recently publishedThese human data support recently published experimental studies, revealing endocrine functions ofexperimental studies, revealing endocrine functions of osteoblast-derived osteocalcin on glucose and fatosteoblast-derived osteocalcin on glucose and fat homeostasis.homeostasis.
    30. 30. ASBMR Effects ofEffects of bonebone onon fat massfat mass  SA 444 Osteocalcin and Obesity Spagnoli Obese and Post Gastric By-pass patients  SU 461 Osteocalcin and type II Diabetes Nguyen  SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Elderly Swedish Men  SU 225 Osteocalcin gene and Body Fat Mass McGuigan Elderly Swedish Women  SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern
    31. 31. ASBMR SU 225 Osteocalcin gene and Body Fat Mass McGuigan Aim:  To determine the relationship between variation in the osteocalcin gene with bone density, fracture and body fat parameters Methods:  1044 elderly women all 75 years old at baseline Follow-up 9 years
    32. 32. ASBMR SU 225 Osteocalcin gene and Body Fat Mass McGuigan 4 SNPs around Osteocalcin locus on Chr 1, including rs1800247 located in the promoter rs 2842880 in intron 13 rs 933489 in intron 14
    33. 33. ASBMR SU 225 Osteocalcin gene and Body Fat Mass McGuigan • Osteocalcin SNP’s were associated with % total body fat at baseline rs1800247 located in the promoter (p=0.045) rs 2842880 in intron 13 (p=0.009) • No longer significant after correction for height Changes in body fat between baseline and 5 years follow-up The heterozygotes appeared to loose the most fat mass.
    34. 34. ASBMR SU 225 Osteocalcin gene and Body Fat Mass McGuigan Conclusion:  The variation in the osteocalcin gene is linked both to BMD and to fracture in elderly Caucasian women  Interestingly, we can not exclude an independent influence of the variation in the osteocalcin gene on changes in fat mass
    35. 35. ASBMR Effects ofEffects of bonebone onon fat massfat mass  SA 444 Osteocalcin and Obesity Spagnoli Obese and Post Gastric By-pass patients  SU 461 Osteocalcin and type II Diabetes Nguyen  SU 459 Osteocalcin and Fat Mass /Glucose Kindblom Elderly Swedish Men  SU 225 Osteocalcin gene and Body Fat Mass McGuigan Elderly Swedish Women  SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern Elderly
    36. 36. ASBMR SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern Aim: To investigate the relationship between osteocalcin and indicators of the metabolic syndrome Methods: 619 randomly selected 70 years old men and women longitudinal study with examinations at age 70, 76 och 86
    37. 37. ASBMR Results • Osteocalcin increased by 44 percent from 70 to 86 years of age. This increase was related to, but independent of, declining kidney function (cystatin C) increasing PTH. • Inverse correlation was found between: OC and BMD OC and BMI in both sexes at all ages investigated (P<0.05). OC adjusted for BMI: OC and insulin r = -0.11 p<0.01 OC and glucose r = -0.25 p<0.0001 A multiple regression model (diabetes excluded) with osteocalcin as dependent variable showed that glucose, (but not insulin), waist circumference and BMD were independent indirect predictors While PTH, cystatin C and ALP were independent direct predictors of osteocalcin (p <0.001). SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern
    38. 38. ASBMR OC was inversely related to the risk of having bilateral carotoid plaques (OR per SD increase in osteocalcin 0.68 (95% CI 0.47 - 0.97)). The risk for stroke within 15 years after the age of 70 was increased in men with low serum osteocalcin (p<0.01). Low osteocalcin increased the risk of having high waist circumference ( Men > 102 cm, women > 88 cm; OR per SD increase in osteocalcin 0.77 (0.67-0.89). Low osteocalcin predicted the parameters of the metabolic syndrome high waist circumference, (p<0.01) BMI >30, high triglycerides, hypertension diabetes. SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern
    39. 39. ASBMR Conclusion: Low serum osteocalcin predicts high glucose and carotid plaques and indicators of the metabolic syndrome. SA 198 Osteocalcin and Carotid Plaques / Metabolic Syndrome Waern
    40. 40. ASBMR bone regulates the energy homeostasis ASBMR 2008 osteocalcin
    41. 41. ASBMR Central Regulation of BoneCentral Regulation of Bone RemodelingRemodeling interaction between bone and braininteraction between bone and brain Rosen 2008 Cell Metab Baldock et al 2007 Lundberg et al 2007 Sato et al 2007 Lee et al 2007
    42. 42. ASBMR Met dank aan de Nederlandse collegae voor de leerzame discussies tijdens de ASBMR
    43. 43. ASBMR
    44. 44. ASBMR  Diabetic subjects had lower plasma osteocalcin (-21.7 %, p< 0.001)Diabetic subjects had lower plasma osteocalcin (-21.7 %, p< 0.001) than non-diabetic subjects.than non-diabetic subjects.  For both all subjects and non-diabetic subjects, plasma osteocalcinFor both all subjects and non-diabetic subjects, plasma osteocalcin was clearly inversely related to BMI, fat mass and plasma glucosewas clearly inversely related to BMI, fat mass and plasma glucose (p< 0.001), while it was not associated with height or lean mass.(p< 0.001), while it was not associated with height or lean mass.  Plasma osteocalcin explained a substantial part (6.3%) of thePlasma osteocalcin explained a substantial part (6.3%) of the variance in plasma glucose while it associated moderately withvariance in plasma glucose while it associated moderately with serum insulin.serum insulin.  Multiple linear regression models adjusting for serum insulin and fatMultiple linear regression models adjusting for serum insulin and fat mass demonstrated that plasma osteocalcin was an independentmass demonstrated that plasma osteocalcin was an independent negative predictor of plasma glucose (p< 0.001).negative predictor of plasma glucose (p< 0.001).
    45. 45. ASBMR Methods and population 619 randomly selected 70 years old men and women longitudinal study with examinations at age 70, 76 och 86. BMD was measured in calcaneus with dual photon absorptiometry and osteocalcin was analysed by a double-antibody radioimmuno-assay. Serum was sampled after 10 hours fasting and non-smoking in the morning. Extra- and intracranial circulation was examined by means of duplex sonography and Transcranial Doppler techniques in 142 subjects at age 78.

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