PTHrP promotes subchondral bone formation in TMJ-OA / 国际口腔科学杂志·英文版

PTH-related peptide (PTHrP) improves the bone marrow micro-environment to activate the bone-remodelling, but the coordinated regulation of PTHrP and transforming growth factor-β (TGFβ) signalling in TMJ-OA remains incompletely understood. We used disordered occlusion to establish model animals that recapitulate the ordinary clinical aetiology of TMJ-OA. Immunohistochemical and histological analyses revealed condylar fibrocartilage degeneration in model animals following disordered occlusion. TMJ-OA model animals administered intermittent PTHrP (iPTH) exhibited significantly decreased condylar cartilage degeneration. Micro-CT, histomorphometry, and Western Blot analyses disclosed that iPTH promoted subchondral bone formation in the TMJ-OA model animals. In addition, iPTH increased the number of osterix (OSX)-positive cells and osteocalcin (OCN)-positive cells in the subchondral bone marrow cavity. However, the number of osteoclasts was also increased by iPTH, indicating that subchondral bone volume increase was mainly due to the iPTH-mediated increase in the bone-formation ability of condylar subchondral bone. In vitro, PTHrP treatment increased condylar subchondral bone marrow-derived mesenchymal stem cell (SMSC) osteoblastic differentiation potential and upregulated the gene and protein expression of key regulators of osteogenesis. Furthermore, we found that PTHrP-PTH1R signalling inhibits TGFβ signalling during osteoblastic differentiation. Collectively, these data suggested that iPTH improves OA lesions by enhancing osteoblastic differentiation in subchondral bone and suppressing aberrant active TGFβ signalling. These findings indicated that PTHrP, which targets the TGFβ signalling pathway, may be an effective biological reagent to prevent and treat TMJ-OA in the clinic.

Hipercalcemia maligna en pacientes con tumores neuroendocrinos. Reporte de 2 casos de tumores pancreáticos productores de péptido relacionado con hormona paratiroidea / Malignant hypercalcaemia in patients with neuroendocrine tumours. Report of 2 cases of parathyroid hormone-related peptide-secreting pancreatic tumours

Resumen La hipercalcemia maligna mediada por péptido relacionado con hormona paratiroidea (PR-PTH) es una manifestación poco común en tumores neuroendocrinos. Presentamos dos pacientes con tumores neuroendocrinos de páncreas con metástasis a hígado pero sin compromiso óseo en quienes se evidenció hipercalcemia maligna asociada a elevación de PR-PTH, con PTH suprimida. En ambos casos se logró normalizar temporalmente la calcemia con el uso de análogos de somatostatina, pero durante la evolución se requirió adición de bisfosfonatos en uno de ellos. Con la discusión de estos casos, la revisión de la literatura y de los casos similares publicados esperamos contribuir al mejor conocimiento de esta enfermedad.

Abstract Parathyroid hormone-related peptide-mediated hypercalcaemia (PTH-rp) is rare in patients with neuroendocrine tumours. The clinical cases are thus presented on two patients with pancreatic neuroendocrine tumours with liver metastases, but without bone involvement and with hypercalcaemia associated with elevated PTH-rp and with PTH suppressed. In both cases, it was possible to temporarily bring the calcium levels back to normal with the use of somatostatin analogues, but during the course of the disease, the addition of bisphosphonates was required in one of them. With the discussion of these cases and the review of the literature and similar published cases, it is hoped to contribute to provide better knowledge of this disease.

Parathyroid Hormone-Related Protein in the Hand or Out of Hand?

No abstract available.

Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism

BACKGROUND: Autosomal-dominant brachydactyly type E is a congenital abnormality characterized by small hands and feet, which is a consequence of shortened metacarpals and metatarsals. We recently encountered a young gentleman exhibiting shortening of 4th and 5th fingers and toes. Initially, we suspected him having pseudopseudohypoparathyroidism (PPHP) because of normal biochemical parameters, including electrolyte, Ca, P, and parathyroid hormone (PTH) levels; however, his mother and maternal grandmother had the same conditions in their hands and feet. Furthermore, his mother showed normal biochemical parameters. To the best of our knowledge, PPHP is inherited via a mutated paternal allele, owing to the paternal imprinting of GNAS (guanine nucleotide binding protein, alpha stimulating) in the renal proximal tubule. Therefore, we decided to further analyze the genetic background in this family. METHODS: Whole exome sequencing was performed using genomic DNA from the affected mother, son, and the unaffected father as a negative control. RESULTS: We selected the intersection between 45,490 variants from the mother and 45,646 variants from the son and excluded 27,512 overlapping variants identified from the father. By excluding homogenous and compound heterozygous variants and removing all previously reported variants, 147 variants were identified to be shared by the mother and son. Variants that had least proximities among species were excluded and finally 23 variants remained. CONCLUSION: Among them, we identified a defect in parathyroid hormone like hormone (PTHLH), encoding the PTH-related protein, to be disease-causative. Herein, we report a family affected with brachydactyly type E2 caused by a novel PTHLH mutation, which was confused with PPHP with unclassical genetic penetrance.

Effects of Serum Albumin, Calcium Levels, Cancer Stage and Performance Status on Weight Loss in Parathyroid Hormone-Related Peptide Positive or Negative Patients with Cancer

BACKGROUND: A recent animal study showed that parathyroid hormone-related peptide (PTHrP) is associated with cancer cachexia by promoting adipose tissue browning, and we previously demonstrated that PTHrP predicts weight loss (WL) in patients with cancer. In this study, we investigated whether prediction of WL by PTHrP is influenced by clinical factors such as serum albumin, corrected calcium levels, cancer stage, and performance status (PS). METHODS: A cohort of 219 patients with cancer whose PTHrP level was measured was enrolled and followed for body weight (BW) changes. Subjects were divided into two groups by serum albumin (cutoff value, 3.7 g/dL), corrected calcium (cutoff value, 10.5 mg/dL), cancer stage (stage 1 to 3 or 4), or PS (Eastern Cooperative Oncology Group 0 to 1 or 2 to 4), respectively. Clinically significant WL was defined as either percent of BW change (% BW) <−5% or % BW <−2% plus body mass index (BMI) < 20 kg/m². RESULTS: After a median follow-up of 327 days, 74 patients (33.8%) experienced clinically significant WL. A positive PTHrP level was associated with a 2-fold increased risk of WL after adjusting for age, baseline BMI, serum albumin, corrected calcium level, cancer stage, and PS. The effect of PTHrP on WL remained significant in patients with low serum albumin, stage 4 cancer, and good PS. Regardless of calcium level, the effect of PTHrP on WL was maintained, although there was an additive effect of higher calcium and PTHrP levels. CONCLUSION: Early recognition of patients with advanced cancer who are PTHrP positive with hypercalcemia or hypoalbuminemia is needed for their clinical management.

Hypercalcemia in a Patient with Systemic Lupus Erythematosus / 대한내과학회지

Hypercalcemia is a common clinical problem. The most frequent causes of hypercalcemia include primary hyperparathyroidism and malignancy; systemic lupus erythematosus (SLE) is a very rare cause of hypercalcemia. Here we describe a case of symptomatic severe hypercalcemia, which developed during a lupus flare. After treatment with intravenous fluids, diuretics, pamidronate, and hemodialysis, calcium levels normalized and were maintained on low-dose prednisolone treatment. To the best of our knowledge, this is the first case of hypercalcemia in a patient with SLE in Korea. Clinicians should consider lupus as a differential diagnosis for patients with severe hypercalcemia.

Clinical Characteristics, Causes and Survival in 115 Cancer Patients with Parathyroid Hormone Related Protein-mediated Hypercalcemia

BACKGROUND: The aim of this study is to determine the proportion of cancers presenting with parathyroid hormone (PTH) related protein (PTHrP)-mediated hypercalcemia, examine the clinical and biochemical characteristics, identify predictive factors for survival. And we also compared those characteristics between solid organ and hematologic malignancy groups. METHODS: Cancer patients with PTHrP-mediated hypercalcemia who were treated at Chonnam National University Hospital in Korea from January 2005 to January 2015 were retrospectively reviewed. RESULTS: Of all 115 patients, solid organ malignancies were the most common etiology (98 cases, 85.2%), with squamous cell carcinoma (50 cases, 43.4%), adenocarcinoma (27 cases, 23.4%). Interestingly, hepatocellular carcinoma (HCC; 18 cases, 15.7%) and cholangiocarcinoma (11 cases, 9.6%) were much more common causes than other previous reports. Hematologic malignancy was less common (17 cases, 14.8%), with multiple myeloma (9 cases, 7.8%) and non-Hodgkin's lymphoma (5 cases, 4.3%). Overall median survival was only 37 days. There was significant difference in median survival between two groups (35 days for solid organ malignancy and 72 days for hematologic malignancy; P=0.015). Cox regression analysis identified age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis as independent predictive factors for survival time. CONCLUSIONS: PTHrP-mediated hypercalcemia was most frequently caused by solid organ malignancy. However, HCC and cholangiocarcinoma were important causes of PTHrP-mediated hypercalcemia may be due to geographic differences in cancer incidence in Korean population. Age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis were independent poor predictive factors for survival time.

Hypercalcemia as Initial Presentation of Metastatic Adenocarcinoma of Gastric Origin: A Case Report and Review of the Literature

Hypercalcemia of malignancy due to metastatic gastric adenocarcinoma is extremely rare; in fact, to the best of our knowledge, only three case reports of hypercalcemia associated with metastatic gastric adenocarcinoma have been published in the literature to date. Herein, we report a rare case involving a 61-year-old African-American female who had hypercalcemia at initial presentation and who was later diagnosed with poorly differentiated gastric adenocarcinoma with extensive liver metastases, without bone involvement. She was found to have elevated parathyroid hormone-related peptide and normal parathyroid hormone levels. Despite aggressive treatment, she died within a few months of diagnosis.

Canine hypoparathyroidism: case report / Hipoparatireoidismo canino: relato de caso

Primary hypoparathyroidism is an uncommon endocrinopathy in dogs, resulting from absolute or relative deficiency in the secretion of parathormone (PTH). The dog presented signs of hypocalcemia, including muscular spasms, tetany and cramps, evolving to tonic-clonic seizures and fever. Emergency therapy for hypocalcemia included glucose physiological solution at 0.45% and calcium gluconate administered intravenously. Diagnosis was confirmed by the presence of hypocalcemia, hyperphosphatemia and a decrease in parathormone (PTH).(AU)

O hipoparatireoidismo primário é uma endocrinopatia incomum em cães, resultante da deficiência absoluta ou relativa na secreção do paratormônio (PTH). O cão apresentava sinais de hipocalcemia, incluindo espasmos musculares, tetania e cãibras que evoluíram para convulsões tônico-clônicas e febre. A terapia de emergência para hipocalcemia incluiu solução glicofisiológica 0,45% e gluconato de cálcio por intravenosa. O diagnóstico foi confirmado pela presença de hipocalcemia, hiperfosfatemia e diminuição do paratormônio (PTH).(AU)

Complete Tumor Resection for a Hepatocellular Carcinoma Secreting Parathyroid Hormone-related Peptide / 대한소화기학회지

Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We report a 71-year-old man who presented with symptoms of vague abdominal discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging studies revealed a large HCC without metastasis. The laboratory findings showed elevated serum calcium level, low intact parathyroid hormone (iPTH) level and elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC and paraneoplastic hypercalcemia. After emergency management of the hypercalcemia, the patient underwent an extended right hemihepatectomy with cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH-rP, and iPTH levels. This case demonstrates that the rare phenomenon of life-threatening hypercalcemia caused by HCC should not be overlooked. These symptoms offer a good opportunity to diagnose HCC early. Radical tumor resection makes it possible to cure patients with PTH-rP-secreting HCC.

Esophageal Cancer Initially Presenting as Severe Paraneoplastic Hypercalcemia Requiring Hemodialysis / 대한소화기학회지

Paraneoplastic hypercalcemia without bone metastasis occurs rarely in esophageal cancer. A 75-year-old man was admitted for general weakness and lethargy. Laboratory data showed high serum calcium level (corrected calcium 14.6 mg/dL), low parathyroid hormone level (3.3 pg/mL) and high parathyroid hormone-related peptide level (3.5 pmol/L). Esophagogastroscopy showed a malignant tumor in the esophagus. Histology showed moderately differentiated squamous cell carcinoma. Bone scan showed no evidence of bone metastasis. Since the patient's calcium levels remained high and mental state did not show improvement despite intravenous fluid therapy, diuretics and intravenous bisphosphonate, hemodialysis was started. After hemodialysis treatment, the serum calcium level subsequently normalized and his mental status improved. Herein, we report a rare case of paraneoplastic hypercalcemia in a patient with esophageal cancer.

Emerging Therapies for Osteoporosis

Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients.

Unusual Manifestation of Intravascular Large B-Cell Lymphoma: Severe Hypercalcemia with Parathyroid Hormone-Related Protein / Journal of the Korean Cancer Association, 대한암학회지

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/computed tomography scan and bone marrow examination, which may be useful for early diagnosis.

Two Cases of Humoral Hypercalcemia of Malignancy in Metastatic Cholangiocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.

Effects of experimentally created unilateral anterior crossbite prosthesis on the expression of parathyroid hormone-related peptide and parathyroid hormone receptor-1 in mandibular condylar cartilage of rat / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the effects of experimentally created unilateral anterior crossbite prosthesis on the expression of parathyroid hormone-related peptide (PTHrP) and parathyroid hormone receptor-1 (PTH1R) in mandibular condylar cartilage of SD rat.</p><p><b>METHODS</b>In experimental groups, the unilateral anterior crossbite metal prosthesis was cemented to the left incisors of the maxilla and mandible of 6-week-old SD rats, respectively. Animals were sacrificed at 2, 4, 8 weeks. Hematoxylin-eosin (HE) staining were carried out for studying the morphological changes of the condylar cartilage. Immunohistochemical staining and real-time polymerase chain reaction (PCR) analysis were performed to detect the levels of expression of PTHrP and PTH1R in the condylar cartilages.</p><p><b>RESULTS</b>The obvious degenerative changes were found in the condylar cartilages in experimental group at 8 weeks. Comparing to the control group, the expression of PTHrP mRNA (P < 0.01) and protein(P < 0.01) in the experimental group were increased, whereas PTH1R mRNA (P < 0.01) and protein (P < 0.01) levels were decreased.</p><p><b>CONCLUSION</b>The expression of PTHrP was increased in the condylar cartilage of rat with unilateral anterior crossbite metal prosthesis but its effects might be limited because of decreased expression of PTH1R in the condylar cartilage. The low level expression of PTH1R should be a part of the constitution of the molecular pathomechanism of temporomandibular joint osteoarthritis (TMJOA)-like lesion.</p>

Heat or radiofrequency plasma glow discharge treatment of a titanium alloy stimulates osteoblast gene expression in the MC3T3 osteoprogenitor cell line

PURPOSE: The purpose of this study was to determine whether increasing the Ti6Al4V surface oxide negative charge through heat (600degrees C) or radiofrequency plasma glow discharge (RFGD) pretreatment, with or without a subsequent coating with fibronectin, stimulated osteoblast gene marker expression in the MC3T3 osteoprogenitor cell line. METHODS: Quantitative real-time polymerase chain reaction was used to measure changes over time in the mRNA levels for osteoblast gene markers, including alkaline phosphatase, bone sialoprotein, collagen type I (alpha1), osteocalcin, osteopontin and parathyroid hormone-related peptide (PTH-rP), and the osteoblast precursor genes Runx2 and osterix. RESULTS: Osteoprogenitors began to differentiate earlier on disks that were pretreated with heat or RFGD. The pretreatments increased gene marker expression in the absence of a fibronectin coating. However, pretreatments increased osteoblast gene expression for fibronectin-coated disks more than uncoated disks, suggesting a surface oxide-mediated specific enhancement of fibronectin's bioactivity. Heat pretreatment had greater effects on the mRNA expression of genes for PTH-rP, alkaline phosphatase and osteocalcin while RFGD pretreatment had greater effects on osteopontin and bone sialoprotein gene expression. CONCLUSIONS: The results suggest that heat and RFGD pretreatments of the Ti6Al4V surface oxide stimulated osteoblast differentiation through an enhancement of (a) coated fibronectin's bioactivity and (b) the bioactivities of other serum or matrix proteins. The quantitative differences in the effects of the two pretreatments on osteoblast gene marker expression may have arisen from the unique physico-chemical characteristics of each resultant oxide surface. Therefore, engineering the Ti6Al4V surface oxide to become more negatively charged can be used to accelerate osteoblast differentiation through fibronectin-dependent and independent mechanisms.

A Case of Adenocarcinoma of the Transverse Colon with Humoral Hypercalcemia of Malignancy

Hypercalcemia is a common electrolyte imbalance in patients with malignancy. Approximately 80% of hypercalcemia is associated with humoral hypercalcemia of malignancy (HHM), but occurs rarely in colorectal carcinomas. A 72-year-old man was admitted with abdominal pain and bowel habit change. Colonoscopy showed a malignant tumor in the transverse colon. Laboratory data showed an elevated serum calcium level (11.6 mg/dL) and elevated parathyroid hormone-related peptide level (12.2 pmol/L). Histology showed poorly differentiated adenocarcinoma. We infused intravenous normal saline, furosemide and pamidronate. The serum calcium level was subsequently normalized. However, the patient died from cancer progression 10 days later. With a review of the relevant literature, we report a case of adenocarcinoma of the transverse colon with HHM.

A Case of Familial Hypocalciuric Hypercalcemia Coexisting with Hypothyroidism / 대한내과학회지

Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder characterized by mild asymptomatic hypercalcemia, hypocalciuria, a decreased urinary calcium-creatinine ratio, and normal or elevated parathyroid hormone levels. FHH is caused by an inactivating heterozygous mutation of the calcium-sensing receptor (CaSR) gene. A 62-year-old woman was referred to our center because of inadequate glucose control. Her son had hypercalcemia. Biochemical and endocrine studies showed hypercalcemia, hypocalciuria, a decreased urinary calcium-creatinine ratio, normal parathyroid hormone levels, normal PTH-related peptide levels, decreased free T4, increased TSH, and thyroid antibody positivity. Direct sequencing analyses revealed a heterozygous mutation of G21R at exon 2 and a single nucleotide polymorphism of R990G at exon 7 of the CaSR gene. Here, we report a case of FHH associated with a heterozygous mutation and a single nucleotide polymorphism of the CaSR gene, which coexisted with autoimmune thyroiditis and hypothyroidism. To our knowledge, this is the first such case reported.

Preparation and identification of recombinant adenoviruses carrying short hairpin RNA targeting parathyroid hormone related protein of goat / 生物工程学报

Parathyroid hormone related protein (PTHrP) has important biological functions in calcium metabolism. The aim of this study was to silence the expression of PTHrP by RNA interference and recombinant adenovirus, and to provide a material to investigate the relative functions of PTHrP in goat mammary gland epithelial cell. The Block-iT shRNA interference system was used in this experiment. We designed and synthesized two pairs of complementary single-strand DNA oligonucleotides (shRNA-322/357) targeting two different sites of PTHrP mRNA. Then the oligonucleotides were inserted into shuttle vector pENTR/CMV-GFP/U6. After detection of the interference efficiency by Western blotting, we chose pENTR/CMV-GFP/U6-322 and adenovirus backbone vector pAD/PL-DEST to produce recombinant vector pAD/PL-DEST/CMV-GFP/U6-322. The first generation recombinant adenovirus particles (AD-PTHrP-322) were produced and further amplified by transfecting HEK-293 cells. The titer of the recombinant adenovirus reached 2.0 x 1(9) PFU/mL determined by TCID50 assays. The result of real-time quantitative PCR indicated that mRNA expression levels of gene were reduced 29.2%, 68.1% and 82.6% (P < 0.05), respectively, when goat mammary gland epithelial cells were infected with AD-PTHrP-322 after 24, 48 and 72 h, in which PTHrP. Western blotting also showed that the expression of PTHrP was reduced by infecting the cells with AD-PTHrP-322. AD-PTHrP-322 has been proved with significant interference effect on expression of PTHrP.

Inhibitory acting mechanism of psoralen-osthole on bone metastasis of breast cancer--an expatiation viewing from OPG/RANKL/RANK system / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To find the optimal proportion of Composite Fructus Psoralea and Fructus Cnidii (CFPC) for inhibiting the bone metastasis of breast cancer by way of exploring its acting mechanism viewing from OPG/RANKL/RANK system.</p><p><b>METHODS</b>The human bone metastasis of breast cancer model was established by injecting tumor cells of MDA-MB-231BO cell line into the left cardiac ventricle of nude mice. The modeled mice were randomly divided into seven groups: the blank group administered with normal saline by gastrogavage, the positive control group with zoledronic acid via peritoneal injection, and the 5 tested group with CFPC in different proportions of Fructus Psoralea and Fructus Cnidii, i.e., (A, 4:0; B, 3:1; C, 1:1; D, 1:3, and E 0:4), given by gastric infusion. The treatment started from 1 week after modeling and lasted for six weeks. By the end of the experiment, the metastatic foci in bone were imaged by radionuclide tracing method and X-ray photograph, and separated for detecting gene and protein expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), interleukin-8 (IL-8), parathyroid hormone-related protein (PTHrP), macrophage colony stimulating factor (MCSF) by Real-time PCR and Western blot respectively.</p><p><b>RESULTS</b>Inhibition of bone metastasis gene was displayed to some extent in all the tested groups treated with CFPC, showing an increased level of OPG mRNA expression (It was 60.343 +/- 6.274 in the tested group C), and decreased mRNA expressions of IL-8, PTHrP, MCSF, RANKL (218.010 +/- 12.802, 232.399 +/- 14.354, 319.831 +/- 5.322, and 195.701 +/- 4. 862, respectively in the tested group C). The optimal effect was shown in the tested group C, showing significant difference to that in the blank group (P < 0.01). Meanwhile, the OPG in the bone metastatic foci could be up-regulated and protein expressions of RANKL/IL-8/PTHrP/MCSF down-regulated in all the tested groups. The optimal effect was shown in the tested group C, with significant difference from those of the normal saline group.</p><p><b>CONCLUSION</b>CFPC could inhibit the bone metastasis of breast cancer through activating OPG/RANKL/RANK pathway. Among different proportions of Fructus Psoralea and Fructus Cnidii, 1:1 was the best one.</p>