Liaison® 25(OH)
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維他命D合成
Synthesis of Vitamin D
Physiology of 1,25(OH)2 vitamin D
Calcium and phosphate homeostasis (CKD / FGF-23) 鈣磷平衡
Bone Remodeling cycle
Metabolic Bone disorders (Drug Therapy) 代謝性骨頭疾病
Clinical background of 1,25(OH)2 vitamin D
Challenges in 1,25(OH)2 vitamin D measurement
Novel 1,25(OH)2 Assay format
BAP (Bone Alkaline Phosphatase ) Assay
Advantage of Bone turnover marker
Vitamin D assay in Reproductive system 生殖系統中的維生素D檢測
維生素D的合成
Synthesis of Vitamin D
Physiology of 1,25(OH)2 D
‧ skin , food ,liver, parathyroid gland, kidney, bone, and small intestine
all play a role
‧ The major form of Vitamin D, 25 (OH) Vitamin D(Calcidiol), has a
limited biological activity.
‧ 1,25(OH)2 Vitamin D(Calcitriol) is a biologically active form
‧ 1,25 (OH)2 vitamin D controls calcium homeostasis
in body by targeting intestines and bones
Physiology of 1,25(OH)2 D
Targeting :
Intestine : 腸道： 增加腸道對鈣和磷酸鹽的吸收
increase absorption of calcium and phosphate from the intestine
Bone
: 骨頭： 增加鈣和磷酸鹽的骨吸收
increase bone resorption of calcium and phosphate
Regulation : 調節 : PTH功能可以增加血清鈣，但會減少血清磷酸鹽
recall PTH functions to increase serum calcium , but
decrease serum phosphate
Physiology of 1,25(OH)2 D
1,25(OH)2 D regulates PTH secretion from the parathyroid gland
through negative feedback control
Calcium homeostasis
Parathyroid hormone
(PTH)
‧ released by low plasma calcium
‧ stimulates bone resorption
刺激骨吸收
(PTH receptor is on the osteoblasts which secretes IL-1 to activated osteoclasts)
‧ prevents calcium excretion by kidneys.
‧ stimulates calcitriol synthesis.
刺激骨吸收 - >骨形成
1,25-(OH)2-Vit. D (Calcitriol) ‧ stimulates bone resorption-> bone formation
‧ stimulates intestinal calcium absorption. 刺激腸道鈣吸收
Physiology of PTH
Phosphate homeostasis
Parathyroid hormone
(PTH)
‧ inhibits phosphate reabsorption in proximal
tubular cell 抑制近端小管的磷酸鹽再吸收
Fibroblast growth factor 23
(FGF23)
‧
‧
‧
‧
polypeptide , synthesized by the osteoblasts
involved in the calcification of bone matrix
acts on the kidney
decreases serum inorganic phosphate
by inhibiting renal phosphate reabsorption and
1,25.(OH)2 D (calcitriol) production
Chronic Kidney Disease (CKD)
Markers
PTH
1,25 (OH)2
Vitamin D
FGF-23
Effect
?decrease phosphate reabsorption 減少磷酸鹽再吸收
?increase calcium reabsorption 增加鈣再吸收
?increase intestinal absorption of calcium and phosphate
?suppress PTH production 抑制PTH的產生
?facilitate excretion of phosphate
?promote calcitriol deficiency
增加腸道對鈣
和磷酸鹽的吸收
Bone Remodel
Bone resorption begins when RANKL on the Osteoblasts
membrane activates the RANK protein on the cell membrane
of the Pre-Osteoblasts
Bone Remodeling Cycle
Bone resorption and bone formation are
Not separated, Not independently regulated process.
Metabolic bone disorders
‧ Normal bone
- bone resorption or degradation is balanced by bone formation
‧ Osteoporosis (low bone mass and abnormal bone microarchitecture)
骨質疏鬆症
（低骨量和異常的骨微結構）
- the rate of resorption exceeds the rate of foemation
Causes:
高骨轉換/內分泌紊亂（原發性和繼發性甲狀旁腺功能亢進）
high bone turnover / endocrine disorder(primary and secondary hyperparathyroidism)
osteomalacia / renal failure / gastrointestinal disease(malabsorption syndrome) /
long-term corticosteroid therapy /multiple myoloma / cancer metastatic to the bones
骨軟化
/腎功能衰竭/
胃腸疾病（吸收不良綜合徵）/
長期皮質類固醇治療/
多發性骨髓瘤/
癌症轉移到骨骼
‧ Paget’s disease (a condition of abnormal bone formation)
Causes:
excessive rates of bone remodeling , results in
local lesions of abnormal bone matrix which results in fractures or neurological
involvement.
骨質重塑率過高，導致骨基質異常的局部病變導致骨折或神經系統疾病
Metabolic bone disorders
佝僂病（導致兒童骨骼軟弱或軟骨的病症）
‧ Rickets (a condition that results in weak or soft bones in children)
- the most common cause is vitamin D deficiency
VDDR I :
a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1 alpha-hydroxylase.
VDDR II :
a spectrum of intracellular vitamin D receptor (VDR) defects
低磷血症性佝僂病（X連鎖低磷血症性佝僂病）
‧ Hypophosphatemic rickets (X-linked hypophosphatemic rickets)
- a form of rickets that is characterized by low serum phosphate levels and
resistance to treatment with ultraviolet radiation or vitamin D ingestion
- circulating FGF-23 concentrations have been shown to be 5 times higher
in XLH patients, resulting in significant phosphaturia.
Metabolic bone disorders
Disorders caused by drug therapies:
藥物治療引起的疾病
‧ immunosuppressive drugs for treating cancer and organ transplants
‧ heparin, used in kidney dialysis
‧ phenytoin (Dilantin.) for epilepsy
( phenobarbital / rifampicin which induce hepatic P450 enzyme to accelerate
the catabolism of Vitamin D )
‧ glucocorticoids (corticosteroids) for rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE) and asthma
‧ aluminium-containing antacids
Drug therapies for metabolic bone diseases
Clinical background of 1,25 Dihydroxyvitamin D
1,25 (OH)2 D is the active form of Vitamin D, its production is tightly
regulated through concentration of serum calcium, phosphorus and PTH.
‧ Low levels can be found in CKD, Vit D dependant rickets type 1,
hypophosphatemic rickets, hypoparathyroidism
‧ High levels in Vit D dependant rickets type 2, Sarcoidosis, RA, IBD,
primary hyperparathyroidism
*
Challenges in 1,25 Dihydroxyvitamin D measurement
Until now, all assays required a long, manual, operator dependent
pre-analytical step due to the following facts:
‧ The molecule circulates in low amounts
The blood levels of 1,25(OH)2 D being 100 to 1000 less than 25 OH D.
(pg/mL concentration vs ng/mL concentrations)
‧ Similarity with its metabolic precursor, 25-OH Vitamin D
*
Novel Assay format
*
LIAISONR XL 1,25 Dihydroxyvitamin D – A paper
*
Key messages
*
LIAISONR XL 1,25 Dihydroxyvitamin D – Benefits
*
Bone and Mineral panel
*
LIAISONR XL BAP OSTASE
骨特異性鹼性磷酸?（BAP）
‧ Bone-specific
alkaline phosphatase (BAP) , a glycoprotein that is found
on the surface of osteoblasts.
‧ Reflects
the biosynthetic activity of these bone-forming cell.
反映骨形成細胞的生物合成活性
‧ Has
shown to be a sensitive and reliable indicator of bone metabolism.
已被證明是一種敏感而可靠的骨代謝指標
*
LIAISONR XL BAP OSTASE
‧ Increased serum levels of BAP : BAP 上升
(in conditions characterized by excessive bone turnover)
停經後婦女/
骨質疏鬆症/
佩吉特病/
甲狀腺毒症/
- postmenopausal women/ osteoporosis/ Paget’s disease/ thyrotoxicosis /
甲狀旁腺功能亢進
hyperparathyroidism / metastatic cancer, and are associated with
rapid bone loss
‧ BAP
levels decrease following anti-resorptive therapy in a
dose-dependent manner. BAP 下降 抗癲癇治療
‧ BAP
identifies rapid bone losers, and accurately monitors the efficacy
of hormone replacement-, bisphosphonate-, PTH analogue- and
growth hormone-therapies
*
Advantage of Bone turnover marker
‧ To
rapidly identify therapy responders and non-responders
(detectable and significant changes in bone mineral density (BMD) take 18 to 24 months to
develop, bone turnover marker takes 3-6 months after starting anti-resorptive therapy)
‧ To
assess therapy efficacy and to determine the optimal therapy and
dose of treatment.
‧ Biochemical bone marker
reflect the whole-body rates of bone turnover,
the combined measurement of bone marker and BMD provides more
information on overall bone loss than BMD measurement at specific
skeletal sites alone.
*
VDR
The cellular effect of
vitamin D is mediated
through the intra-nuclear
vitamin D receptor (VDR)
Pandemic of Vitamin D deficiency
Vitamin D deficiency related diseases :
兒童佝僂病
‧ Rickets in Children
‧ Osteoporosis, Osteomalacia 骨質疏鬆症
‧ Cancer
‧ Type II Diabetes 第II型糖尿病
‧ Cardiovascular disease 心血管疾病
‧ Auto Immune Diseases 自體免疫疾病
‧ Parkinson’s disease 帕金森氏病
‧ Reproductive system 生殖系統
維生素D缺乏相關疾病
Vitamin D and Reproductive system
‧ In the last few years , many researchers have studied the association
of Vitamin D and reproductive health but there is still no single
consensus on its influence in reproductive health.
‧ While it is s general observation that optimal level of Vitamin D
is essential in PCOS, Endometriosis, Male infertility and IVF
technique.
‧ but there has been no significant correlation between Vitamin D level
and ovulation stimulation or embryo development.
Vitamin D and Female Reproduction
PCOS
(Polycystic ovary syndrome)
多囊卵巢症候群
‧ Inverse association of serum Vit D and circulating androgens
and insulin resistance in women with PCOS.
‧ Vit D supplementation improves menstrual frequency and
metabolic syndromes.
維生素D補充可改善月經頻率和代謝症候群。
PCOS: 高雄激素
多毛症
卵巢和月經不調
胰島素抵抗
hyper-androgenism / hirsutism / ovalatory and menstrual irregulations /insulin resistence /
low pregnancy success rate / obesity / elevated cardiovascular disease risk
低妊娠成功率
肥胖
心血管疾病風險升高
Vitamin D and Female Reproduction
Endometriosis
子宮內膜異位症
‧ Higher 25(OH)D levels in women with endometriosis than control.
- extrarenal site of Vit D synthesis and action : endometrial tissue
- similar VDR polymorphism genotype
Vitamin D and Male Reproduction
Male infertility
男性不育
‧ Vitamin D metabolism enzymes (CYP24A1) are describes in the
human testis, the ejaculatory tract , mature spermatozoa and in the
Leydig cells.
‧ Observed significantly reduced CYP24A1-expressing spermatozoa
in the subfertile man compared with the healthy group.(P<0.001)
‧ Man with Vit D deficiency displayed a lower percentage of motile
and morphologically normal sperm compared with Vit D sufficient
subjects. 維生素D缺乏的人 精子表現出較低的運動百分比和正常的精子形態
Vitamin D and Female Reproduction
IVF
(In Vitro Fertilization)
體外受精
‧ High 25(OH)D levels are associated with higher clinical pregnancy rate.
‧ No significant difference.
‧ High follicular fluid 25(OH)D levels : lower clinical pregnancy rate.
Vitamin D and Female Reproduction
AMH
抗穆勒氏管荷爾蒙
‧ Premenopausal women where divided in 3 groups: age < 35 ,
age 35-39 , age > 40. For the youngest women AMH was
negatively correlated with Vit D, whereas for the oldest women the
relationship was reversed. The mean age at which the relationship
was reversed was 35.
‧ AMH levels exhibited seasonal variation in women , with an 18%
decrease in AMH levels in winter compared with summer. Vit D
prevented seasonal AMH change. Vit D may be a positive regulator
of AMH production in adults.
Vitamin D and Reproductive system
Large studies including all ethnic and racial groups would be
required to proclaim the role of Vitamin D in infertility .
Thank you for tour attention
