Table 2.
Preclinical (in vitro and in vivo) and clinical studies on PLT functions/features and growth factor in PLTs during osteoporosis.
| Reference | Aim | Study Design | Methodology | Platelet Function | Link Between Platelet and Osteoporosis | Main Results |
|---|---|---|---|---|---|---|
| In vitro studies | ||||||
| Pountos et al. 2010 [39] | Effect of BMP-2, BMP-7, PTH, and PDGF on proliferation and osteogenic differentiation of OP MSCs | MSCs isolated from trabecular bone of 10 OP patients (4 male and 6 female) treated with a 106 range of concentrations (0.001 to100 ng/mL) of PDGF-BB | Functional assays of proliferation and osteogenic differentiation | PDGF-BB | PDGF-BB have a positive effect on osteogenic differentiation of OP MSCs | MSC proliferation stimulated by BMP-7 and PDGF-BB |
| In vivo studies | ||||||
| Xie et al. 2014 [40] | Role of PDGF-BB in OVX mice | OVX C57BL/6 female mice injected with 1 μg PDGF-BB into the bone marrow cavity | Micro-CT, immunocytochemistry, immunofluorescence and histomorphometry. | PDGF-BB | Local PDGF-BB administration can temporally increase angiogenesis and spatially promote bone formation to couple angiogenesis with osteogenesis in bone modeling and remodeling | ↑PDGF-BB concentrations, VEGF concentrations, vessel volume, CD31hi Emcnhi cells, proliferation of endothelial cells in metaphysis, trabecular bone volume, thickness and number, cortical bone thickness, serum osteocalcin concentration in OVX mice treated with PDGF-BB |
| Zhang et al. 2014 [41] | Effect on osteointegration of nanotube arrays loaded with rhPDGF-BB | OVX rat femur implantation: - oxalic acid-etched titanium rods - titanium rods modified with TiO2 nanotube arrays - PDGF group (titanium rods immersed in 100 μg/mL rhPDGF-BB) - PDGF + Vacuum extraction (vacuum pump -PDGF + Vacuum group-for 10 min) |
Static and dynamic histomorphometry and biomechanical test | PDGF-BB | Immobilization of rhPDGF-BB on nanotube arrays as implant surface modification strategy in orthopedic applications in osteoporotic patients | rhPDGF-BB immobilized on the nanotube surface ↑ new bone formation and osseointegration |
| Tang et al. 2017 [42] | Association between low plasma PDGF-BB levels and oestradiol | Sprague–Dawley rat: -Sham -OVX -OVX+oestradiol (100 mg/kg/d) -OVX+PDGF-BB (1mg/3 d/wk) |
Plasma oestradiol and PDGF-BB levels measured using ELISA kits | PDGF-BB | Plasma PDGF-BB levels play a major role in OVX rats | ↓PDGF-BB levels in OVX rats than SHAM group. Oestradiol replacement ↑plasma PDGF-BB levels, while PDGF-BB systematic treatment not affect plasma estradiol levels |
| Clinical studies | ||||||
| Kim et al. 2011 [43] | Association between peripheral blood cell (PLT, WBC, RBC) counts BMD | Case-control study 17 OP patients 167 osteopenic patients 154 control subjects |
DXA, biochemical parameters | PLTs count | Positive relationship between blood cell counts and BMD | WBC, RBC and PLT counts significantly associated with BMD |
| Li et al. 2012 [44] | Relationship between PLT count, MPV, and BMD |
Case-control study 111 OP patients 171 osteopenic patients 128 control subjects |
DXA, biochemical parameters | PLTs count and MPV | MPV negatively correlated with BMD | Negative correlation between MPV and the lumbar and femoral neck BMD. Univariate and multivariate analysis: MPV significantly associated with lumbar spine L2–L4 BMD and femoral neck BMD |
| D’Amelio et al. 2012 [45] | Correlation between PLTs vitamin D receptor expression and OP | Case-control study 77 postmenopausal OP patients 33 healthy control of childbearing age 49 healthy control men 11 healthy women matched with patients for age and postmenopausal period |
DXA, markers of bone metabolism and vitamin D receptor levels | PLTs vitamin D receptor expression | Reduced level of PLT vitamin D receptor is correlate to OP | ↓PLTs vitamin D receptor expression in OP patients respect to healthy postmenopausal controls. PLTs vitamin D receptor not influenced by gender. PLTs vitamin D receptor predict 65% of the BMD variation. |
| Akbal et al. 2014 [32] | Correlation between BMD and MPV and PDW | Case-control study 30 OP patients 30 osteopenic patients 20 control subjects |
DXA, full laboratory test | MPV PDW |
Significant role of PDW and MPV in the postmenopausal OP development | ↓MPV and PDW in OP than the normal BMD patients. PDW positively correlated with FTT and L1–4T scores. Age and PDW independently related to FTT and LTT scores. |
| Kim et al. 2015 [34] | Association between plasma PAF, OP vertebral fracture and BMD | Case-control study 73 OP patients with vertebral fracture 73 OP patients without vertebral fracture |
Radiography, DXA, biochemical parameters, plasma PAF concentration | PAF | Plasma PAF levels inversely correlated with BMD | 34.6% ↑ plasma PAF levels in postmenopausal women with vertebral fracture than subjects without vertebral fracture |
| Aypak et al. 2016 [46] | Correlation between BMD and MPV | Case-control study 126 OP patients 37 osteopenic patients 12 control subjects |
DXA, laboratory tests including complete blood count (CBC), calcium, phosphorus, serum 25 hydroxyvitamin D (25OHD), and intact parathormone (iPTH) |
MPV | MPV correlated with BMD in postmenopausal OP women. | MPV significantly associated with BMD in normal weight and overweight-obese OP patients. |
| Tang et al. 2017 [42] | Association between low plasma PDGF-BB levels and oestradiol in postmenopausal OP | Case-control study 28 postmenopausal OP patients 69 control young woman 24 age-matched women |
DXA, plasma oestradiol and PDGF-BB levels | PDGF-BB | Plasma PDGF-BB levels maintained by oestrogen in normal young women and play a major role in postmenopausal OP |
↓plasma oestradiol and PDGF-BB levels in postmenopausal women, especially in OP patients. PDGF-BB levels were positively correlated with oestradiol levels and inversely correlated with age |
| Vural et al. 2017 [47] | Correlation between PLT functions, vitamin D and BMD |
Case-control study 124 OP patients 151 osteopenic patients 87 control subjects |
DXA, biochemical parameters | MPV | No correlation between MPV and OP. MPV considered a less important indicator in serum 25-hydroxyvitamin D levels and OP | No difference in MPV and PLT counts between groups. No correlation between MPV and serum 25-hydroxyvitamin D levels. Correlation between PLT count and lumbar spine (L1–4) T score |
| Koseoglu et al. 2017 [48] | Correlation between PLT/lymphocyte ratio and low BMD in postmenopausal woman |
Case-control study 179 OP and osteopenic patients 32 control subjects |
DXA, biochemical parameters | PLT/lymphocyte ratio | PLT/lymphocyte ratio as new inflammatory marker for bone loss and low BMD | ↑PLT/lymphocyte ratio in OP and osteopenic patients than in the control subjects. Negative correlation between lumbar and femur neck BMD and PLT/lymphocyte ratio |
| Eroglu et al. 2019 [33] | Correlation between PLT/lymphocyte and BMD |
Case-control study 48 OP patients 112 osteopenic patients 92 control subjects |
DXA, biochemical parameters | PLT/lymphocyte ratio | Negative correlation Between PLT/lymphocyte and BMD |
↑PLT/lymphocyte ratio in OP and osteopenic patients. |
MPV: mean platelet volume; PDW platelet distribution width; FTT: femur total T; L1–4T: lumbar 1–4T; PAF: platelet-activating factor; WBC: peripheral blood white blood cell RBC: red blood cell.