ABSTRACT
The bone formation promoter recombinant human parathyroid hormone 1-34 [PTH (1-34)] has a short half-life and low bioavailability. In this study, we prepared a biodegradable and temperature-sensitive hyaluronic acid-poly-N-isopropyl acrylamide (AHA-g-PNIPAAm), and further investigated its effects of PTH (1-34) release and cell behavior as drug carrier. The structure of AHA-g-PNIPAAM was confirmed by hydrogen nuclear magnetic resonance spectroscopy and infrared spectroscopy. Next, PTH (1-34) loaded thermo-sensitive hydrogels were prepared by physical swelling method and their stability was investigated. The morphology of hydrogel was observed by scanning electron microscope. The minimum critical transition temperature and drug release behavior of hydrogels were investigated by ultraviolet spectrophotometry. The tetrazolium-based colorimetric assay (MTT assay) was used to investigate the toxicity and proliferation effects of PTH (1-34)-loaded thermo-sensitive hydrogel on mouse mononuclear macrophage RAW264.7 and mouse precranial osteoblasts MC3T3-E1. The effect of PTH (1-34)-loaded thermo-sensitive hydrogel on the differentiation of RAW264.7 was investigated by the tartrate-resistant acid phosphatase assay. The results showed that the PTH (1-34)-loaded thermo-sensitive hydrogel prepared in this study displayed regular three-dimensional honeycomb structure, and had good stability, thermo-sensitivity and sustained and controlled release properties, which could promote the proliferation of MC3T3-E1 cells more effectively and inhibit the differentiation of RAW264.7 into osteoclasts.
ABSTRACT
BACKGROUND: Recombinant human parathyroid hormone 1-34 (rhPTH 1-34), also known as teriparatide, is the amino terminal fragment of parathyroid hormone. Teriparatide, as a bone anabolic drug, has become a research hotspot because it can directly stimulate new bone formation and increase bone mass. It also attracts attention and application in the oral field due to its strong osteogenesis effect. OBJECTIVE: To review the osteogenic mechanisms, efficacy and safety of teriparatide and its research progress in the oral field. METHODS: The first author searched the PubMed and WanFang databases for relevant literature published over the past two decades. The keywords were “rhPTH(1-34); teriparatide; osteoporosis; stomatology; Jaw; implant-osseointegration; periodontal” in English and Chinese, respectively. Fifty-six eligible articles were finally reviewed. RESULTS AND CONCLUSION: Teriparatide can directly stimulate the formation of osteoblasts in new bone and achieve effective anabolic metabolism. Studies of teriparatide in the oral field have shown good results in promoting implant-osseointegration, periodontal regeneration, bone defect healing and the stability of orthodontics, but increasing high-quality animal experiments and clinical studies are still needed. Future use of parathyroid hormone drugs and their analogues can be combined with bone tissue engineering technology to provide favorable effects in bone repair as well as in oral and maxillofacial repair.
ABSTRACT
Objective:To evaluate the efficacy and safety of rhPTH(1-34)vs. elcatonin.Methods:Sixty patients with primaryOP were randomly divided into two groups according to the ratio of3:1. rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34)20 μg daily for18 months, and the elcatonin group(CT group) was treated with intramuscular injection of elcatonin20U weekly for12 months.Bone mineral density(BMD) of the lumbar spine2-4(L2-4) and femoral neck, serum calcium and phosphorus, urinary calcium, serum bone specific alkaline phosphatase(BSAP), and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ/Cr) were tested at baseline, and6,12, and18 months after treatment.Results:InPTH group, BMD ofL2-4 at6,12, and18 months,BDM of femoral neck at18 month,BSAP at6 and12 months and uCTX-Ⅰ/Cr at6,12 and18 months were all significantly raised.InCT group,BMD ofL2-4at 12 month and that of femoral neck at12 and18 months were significantly elevated, whileBSAP was significantly decreased at12 and18 months, and no significant difference onCTX-Ⅰ/Cr was observed.WhenBMD growth and growth rate between two groups were compared,PTH group had better improvement inL2-4BMD and growth rate thanCT group at6,12, and18 months.BMD growth and growth rate of femoral neck at12 month and its growth at18 month inCT group were higher than inPTH group, but there was no significant difference between two groups regarding the growth rates at18 month.Besides, there were no significant differences regarding the rates of adverse reactions between two groups.Conclusions: rhPTH(1-34), is safe and effective in the treatment of primaryOP.It is superior to elcatonin in improving vertebralBMD at onset time, growth rate and growth range, but inferior to elcatonin atBMD of femoral neck.
ABSTRACT
Objective Recombinant human parathyroid hormone(1-34) [ rhPTH(1-34)] is the unique anabolic substance acting on the skeleton. The efficacy and safety of long-term administration of rhPTH(1-34) in Chinese postmenopausal women have not been evaluated. This study compared the clinical efficacy and safety of rhPTH(1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods A total of453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH(1-34) 20 μg(200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine ( L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover ( serum bone-specific alkaline phosphatase was measured by radioimmunoassay; C-telopeptide/ creatinine ( CTX/ Cr) measured by quantitative sandwich enzyme-linked immunosorbent assay) at 6, 12, and 18 months. Adverse events were recorded. Results rhPTH(1-34) increased lumbar BMD more significantly than that did by elcatonin at 6 months( M6), 12 months (M12), and 18 months(M18; 4. 3% vs 1. 94% , 6. 8% vs 2. 72% , 9. 51% vs 2. 86% , P<0. 01). There was only a small but significant increase of femoral neck BMD at M18(2. 64% , P<0. 01) in rhPTH(1-34) groups. There were greater increases in bone turnover markers in the rhPTH(1-34) group than in the elcatonin group at M6, M12, and M18[serum bone-specific alkaline phosphatase(BSAP) 93. 67% vs -3. 56% , 117. 78% vs -4. 12% , 49. 24% vs-5. 81% , P<0. 01; urinary CTX/ Cr 250% vs -29. 5% , 330% vs -41. 4% , 273 % vs -10. 6% , P<0. 01]. rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5. 36% (6 / 112) in elcatonin group and 3. 23% ( 11 / 341 ) in rhPTH ( 1-34 ) group ( P = 0. 303 ). Both treatments were well tolerated. Hypercaluria(9. 38% ) and hypercalcemia(7. 04% ) in rhPTH(1-34) group was transient and caused no clinical symptoms. Pruritus(8. 21% vs 2. 68, P=0. 044) and redness of injection site(4. 40% vs 0, P=0. 024) were more frequent in rhPTH(1-34). Nausea / vomiting(16. 07% vs 6. 16% , P = 0. 001) and hot flushes(7. 14% vs 0. 59% , P<0. 001) were more common in elcatonin group. Conclusion rhPTH(1-34) treatment was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months treatment. rhPTH(1-34) could ameliorate back pain effectively. The results of the present study indicate that rhPTH(1-34) is an effective, and safe agent in treating postmenopausal women with osteoporosis.
ABSTRACT
Objective To investigate changes in serum sclerostin (SO) in postmenopausal women before and after treatment with recombinant human parathyroid hormone (1-34) [rhPTH (1-34)],and to explore the relationship of serum SO with estradiol (E2),and bone mineral density (BMD).Methods Ninety-five postmenopausal women were divided into normal BMD group (n =41) and osteoporosis group (n =54).Body mass index,alkaline phosphatase (ALP),serum E2,calcium,phosphate,and SO were determined in both groups.The patients in osteoporosis group were treated with rhPTH (1-34) 20 μg/d by subcutaneous injection and oral calcium 500 mg/d for 12 months.Serum calcium,serum phosphate,BMD,serum ALP,serum E2,and sclerostin were determined in osteoporosis group by 6 months and 12 months of treatment.Results (1) Serum level of SO in osteoporosis group was raised significantly as compared with normal BMD group (P ＜ 0.05) ; E2 and BMD were negatively correlated with SO; age and postmenopausal years were positively correlated with SO (P ＜ 0.05).(2) Serum SO was reduced gradually with treatment of rhPTH (1-34) by 6 months and 12 months (P ＜ 0.05).Conclusions Serum SO was increased in postmenopausal women,which was related to E2 and BMD,and was reduced gradually with treatment of rhPTH (1-34).SO may participate in the development of postmenopausal osteoporosis.
ABSTRACT
ObjectiveTo investigate the effect of rhPTH (1-34) and elcatonin on bone metabolism and serum secreted protein acidic and rich in cysteine ( SPARC ) in postmenopausal women with osteoporosis.Methods One hundred and twenty-four postmenopausal women with osteoporosis were randomly divided into 2 groups:One group was treated with recombinant human parathyroid hormone ( 1-34 ) [ rhPTH ( 1-34 ) ] 200 U/d by subcutaneous injection (PTH group,n =89 )and another group was treated with elcatonin 20 U/week by intramuscular injection (CT group,n =35 ) for 12 months.All patients received a basic therapy with oral calcium ( Ca 600 mg+ Vit D3125 U,q..d.).The bone mineral density ( BMD ) of lumbar spine( L2-4 ),the left femoral neck,greater trochanter,and Ward's triangle,serum calcium and phosphate were measured by baseline,6 months' and 12 months.Levels of serum bone-specific alkaline phosphatase( BSAP),serum secreted protein acidic and rich in cysteine (SPARC)were determined by an ELISA assay.ResultsBy 12 months,rhPTH ( 1-34 ) treatment significantly increased the lumbar spine L2-4 BMD 7.9％ (P＜0.05),serum calcium 8.3 ％ ( P＜ 0.05 ),serum BSAP 93.4％ ( P＜ 0.05 ),serum SPARC by 12.6％[ ( 195.68±59.57 vs 173.81 ±81.33 ) pμg/L,P＜0.05 ].Elcatonin therapy increased the lumbar spine L2-4 BMD by 3.2％ (P＜0.05) at the end of 12 months,but elcatonin did not influence serum calcium,BSAP and SPARC.The rhPTH( 1-34 ) increased lumbar spine L2-4 BMD more than elcatonin did at 12 months( P＜0.05 ).ConclusionrhPTH (1-34) could promote the bone anabolism more effectively than elcatonin did.Serum SPARC may play an important role in promoting osteogenesis by rhPTH.