Targeting bone physiology for the treatment of metastatic prostate cancer.

Metastatic prostate cancer has a unique predilection for bone that can lead to significant clinical sequelae, such as fracture and cord compression. This tropism for bone yields not only clinical challenges, but also opportunities to understand the tumor biology in bone and to develop relevant therapeutic strategies. The process by which tumor cells migrate to bone, remain dormant, and then colonize and expand is based on complex interactions between prostate cancer tumor cells and the host microenvironment. This review will provide an overview of these interactions as well as therapies targeting osseous metastases in castration-resistant prostate cancer.

The effects of minimally invasive laser needle system on suppression of trabecular bone loss induced by skeletal unloading.

This study was aimed to evaluate the effects of low-level laser therapy (LLLT) in the treatment of trabecular bone loss induced by skeletal unloading. Twelve mice have taken denervation operation. At 2 weeks after denervation, LLLT (wavelength, 660 nm; energy, 3 J) was applied to the right tibiae of 6 mice (LASER) for 5 days/week over 2 weeks by using a minimally invasive laser needle system (MILNS) which consists of a 100 µm optical fiber in a fine needle (diameter, 130 µm) [corrected]. Structural parameters and histograms of bone mineralization density distribution (BMDD) were obtained before LLLT and at 2 weeks after LLLT. In addition, osteocyte, osteoblast, and osteoclast populations were counted. Two weeks after LLLT, bone volume fraction, trabeculae number, and trabeculae thickness were significantly increased and trabecular separations, trabecular bone pattern factor, and structure model index were significantly decreased in LASER than SHAM (p < 0.05). BMDD in LASER was maintained while that in SHAM was shifted to lower mineralization. Osteocyte and osteoblast populations were significantly increased but osteoclast population was significantly decreased in LASER when compared with those in SHAM (p < 0.05). The results indicate that LLLT with the MILNS may enhance bone quality and bone homeostasis associated with enhancement of bone formation and suppression of bone resorption.

Low-intensity pulsed ultrasound protects subchondral bone in rabbit temporomandibular joint osteoarthritis by suppressing TGF-ß1/Smad3 pathway.

Transforming growth factor ß1(TGF-ß1)/Smad3 pathway promotes the pathological progression of subchondral bone in osteoarthritis. The aim of this study is to determine the effect of low-intensity pulsed ultrasound (LIPUS) on the pathological progression and TGF-ß1/Smad3 pathway of subchondral bone in temporomandibular joint osteoarthritis (TMJOA). Rabbit TMJOA model was established by type II collagenase induction. The left joint in this model was continuously stimulated with LIPUS for 3 and 6 weeks (1 MHz; 30 mW/cm2 ) for 20 min/day. The morphological and histological features of subchondral bone were respectively examined by microcomputed tomography and Safranin-O staining. The number of osteoclasts was quantitatively assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry and Western blot analysis were conducted to evaluate the protein expression of Cathepsin K and TGF-ß1/Smad3 pathway. The results indicated that LIPUS could improve the trabecular microstructure and histological characteristics of subchondral bone in rabbit TMJOA. It also suppressed abnormal subchondral bone resorption and activation of TGF-ß1/Smad3 pathway, characterized by the number of osteoclasts, protein expression levels of Cathepsin K, TGF-ß1, type II TGFß receptor, and phosphorylated Smad3 (pSmad3) were decreased. In conclusion, LIPUS promoted the quality of subchondral bone by suppressing osteoclast activity and TGF-ß1/Smad3 pathway in rabbit TMJOA.

Extracorporeal shock wave therapy induces alveolar bone regeneration.

UNLABELLED: Periodontal inflammation with alveolar bone resorption is a hallmark of periodontitis. We hypothesized that extracorporeal shock wave therapy (ESWT) could promote the regeneration of alveolar bone following Porphyromonas gingivalis-induced periodontitis in rats. Rats were infected with P. gingivalis for 10 wks, which caused alveolar bone resorption. The rats were then treated with a single episode of 100, 300, or 1000 impulses of shock wave on both cheeks at energy levels 0.1 mJ/mm(2). Alveolar bone levels were determined at 0, 3, 6, and 12 wks following ESWT and compared with those in untreated controls. Infected rats treated with 300 and 1000 impulses demonstrated significantly improved alveolar bone levels at 3 wks compared with untreated controls, and the improved levels remained for at least 6 wks in most rats. The results demonstrated effective regeneration of alveolar bone by ESWT and suggested that ESWT should be evaluated as an adjunct in the regeneration of periodontal tissues following periodontal disease. ABBREVIATIONS: ESWT, extracorporeal shock wave therapy; PCR, polymerase chain-reaction.

Hypercalcemia induced with an arotinoid in thyroparathyroidectomized rats. New model to study bone resorption in vivo.

A model of stimulated bone resorption was developed using a synthetic retinoid in thyroparathyroidectomized rats. The retinoid induced an increase in bone resorption and in the number of vertebral subperiosteal osteoclasts. The resulting increase in plasma Ca could be used as an easily measured index of bone resorption. Three bisphosphonates produced a dose-related prevention and reversal of retinoid-induced hypercalcemia. Their potencies were similar to those previously obtained by histomorphometry. Irradiation (600 rad) of the rats prevented hypercalcemia but failed to reverse it, showing that proliferation of osteoclast precursor cells was important in inducing, but not in maintaining, bone resorption. Calcitonin produced similar effects on calcemia and prevented the increase in osteoclast number but failed to reverse the increase, suggesting that it inhibited precursor proliferation. This model represents a new tool to study mechanisms of bone resorption and the action of inhibitors in vivo.

[An experience with combined therapy of radiation and Bonephos for osteolytic metastases of breast cancer]. / Opyt sovmestnogo primeneniia luchevoi terapii i Bonefosa pri lechenii kostnykh osteoliticheskikh metastazov raka molochnoi zhelezy.

A new procedure of conservative treatment (radiation + benephos) is suggested to improve the quality of life of cancer patients with osteolytic metastases. Radiation regimen, dosage, benephos administration methods and characteristics of combined therapy are discussed. The procedure was tested in the course of the treatment of 21 breast cancer patients with osteolytic metastases. According to preliminary results, the treatment is easy to tolerate; it produced stable analgetic effect (2-9 months) in 85.7%, as compared with 42.1% in the control group.

Disappearing bone disease: massive osteolysis of the ribs treated with radiotherapy. Report of a case.

The case of a boy with disappearing bone disease concerning the ribs is reported. The clinical, roentgenographic, immunological and histological studies are described. The patient was treated by radiotherapy. The process of disease stopped in irradiated area of the chest, but five months later appeared beyond that area. The patient was irradiated additionally for the next area and disease was arrested successfully.

Response of lymphangiectasis to radiotherapy.

A 14-year-old girl with lymphangiectasis of the skull causing rapid extensive destruction of the left orbit, zygoma, mandible, sphenoid, and occiput underwent radiotherapy with 2000 rad to the entire skull, mandible, and upper cervical vertebrae. Three years later, progression of the disease has ceased, and the involved bone is slowly remineralizing.

Radiotherapy in massive angiomatous osteolysis (Gorham-Stout's syndrome).

The cases of two young men with the Gorham-Stout's syndrome of massive angiomatous osteolysis are presented. Attempted surgical removal of the pathological angiomatous tissue proved unsuccessful. Telegammatherapy with each patient receiving total focal dose of 40.0 Gy fractionated over a period of 4 weeks resulted in speedy and complete arrest of osteolysis, and in partial recalcification of the bone tissue destroyed. In one patient the favourable condition has been lasting for 9 years, in the other for 8 months from the end of the course of radiotherapy. The authors discuss the cause of a central fracture of the first patient's left acetabulum which was noted 5 years after the radiotherapy. Proceeding from their experience so far, the authors describe radiotherapy in the Gorham-Stout's syndrome as a method of choice, and give a list of the therapeutical principles.

Massive osteolysis in the hand and response to radiotherapy.

We report a case of severe bony and articular destruction in the hand of a 62-year-old woman, secondary to localized vascular proliferation. A short course of radiotherapy (total dose 3000 rad) resulted in rapid relief of symptoms and prevention of further osseous destruction over a 6-year followup period.

[Gorham-Stout syndrome--progressive osteolysis with viscerocranial involvement]. / Gorham-Stout-Syndrom--Progressive Osteolyse mit Befall des Viszerokraniums.

Two rather young patients with spontaneous massive mandible osteolysis are presented, i.e. a woman suffering from a rhinogenous liquor fistula and recurrent meningitides, and a young man. The authors discuss etiology, pathologic anatomy, clinical and radiological course, as well as the combined surgical and radiotherapeutical treatment. The pathologic process shall be stopped by the combination of both therapy methods. A radiation dose of 30 to 50 Gy is recommended.