Summary Reasons for performing study: Bisphosphonates, such as tiludronate, are used to normalise bone metabolism via inhibition of bone resorption. Areas of increased bone resorption and formation are typical lesions in a diseased navicular bone. Objectives: To determine if bone remodelling changes occurring in navicular disease may be corrected with therapies regulating bone metabolism. Methods: We designed a double‐blind, placebo‐controlled clinical trial to compare 2 doses of tiludronate, 0.5 mg/kg and 1 mg/kg bwt administered via daily i.v. injections over 10 days for the treatment of navicular disease. Seventy‐three horses, split into 2 subpopulations of recent and chronic cases, were enrolled to be followed‐up over 6 months. Of these, 33 recent and 17 chronic cases meeting the selection criteria were maintained in the final efficacy analyses. Clinical examinations were videorecorded and reviewed blindly by an independent expert. Results: Horses treated with the higher dose showed optimal improvement of lameness and return to normal level of activity 2–6 months post treatment. The more recent the onset of clinical signs at the time of treatment, the greaterthe efficacy. The treatment did not modify the response to extension and flexion tests. The lower dose failed to significantly improve the condition. Conclusions: Tiludronate efficacy is demonstrated in the treatment of navicular disease at the dose of 1 mg/kg bwt. Potential relevance: Our results support the clinical relevance of bone remodelling changes in the outcome of navicular disease.

IntroductionThe aim of this prospective, randomized, controlled, double-blind study was to evaluate the effects of tiludronate (TLN), a bisphosphonate, on structural, biochemical and molecular changes and function in an experimental dog model of osteoarthritis (OA).MethodsBaseline values were established the week preceding surgical transection of the right cranial/anterior cruciate ligament, with eight dogs serving as OA placebo controls and eight others receiving four TLN injections (2 mg/kg subcutaneously) at two-week intervals starting the day of surgery for eight weeks. At baseline, Week 4 and Week 8, the functional outcome was evaluated using kinetic gait analysis, telemetered locomotor actimetry and video-automated behaviour capture. Pain impairment was assessed using a composite numerical rating scale (NRS), a visual analog scale, and electrodermal activity (EDA). At necropsy (Week 8), macroscopic and histomorphological analyses of synovium, cartilage and subchondral bone of the femoral condyles and tibial plateaus were assessed. Immunohistochemistry of cartilage (matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS5)) and subchondral bone (cathepsin K) was performed. Synovial fluid was analyzed for inflammatory (PGE2 and nitrite/nitrate levels) biomarkers. Statistical analyses (mixed and generalized linear models) were performed with an α-threshold of 0.05.ResultsA better functional outcome was observed in TLN dogs than OA placebo controls. Hence, TLN dogs had lower gait disability (P = 0.04 at Week 8) and NRS score (P = 0.03, group effect), and demonstrated behaviours of painless condition with the video-capture (P < 0.04). Dogs treated with TLN demonstrated a trend toward improved actimetry and less pain according to EDA. Macroscopically, both groups had similar level of morphometric lesions, TLN-treated dogs having less joint effusion (P = 0.01), reduced synovial fluid levels of PGE2 (P = 0.02), nitrites/nitrates (P = 0.01), lower synovitis score (P < 0.01) and a greater subchondral bone surface (P < 0.01). Immunohistochemical staining revealed lower levels in TLN-treated dogs of MMP-13 (P = 0.02), ADAMTS5 (P = 0.02) in cartilage and cathepsin K (P = 0.02) in subchondral bone.ConclusionTiludronate treatment demonstrated a positive effect on gait disability and joint symptoms. This is likely related to the positive influence of the treatment at improving some OA structural changes and reducing the synthesis of catabolic and inflammatory mediators.

In a review of 1037 patients with colorectal cancers, there were 32 patients below the age of 40 years (3 percent). Rectal bleeding and abdominal pain were the most common presenting symptoms. The average delay between the onset of symptoms and treatment was 6.5 months. An analysis of tumors according to Dukes' staging revealed no significant difference between young and elderly patients. The younger patients had a greater frequency of mucinous and poorly differentiated carcinoma. When compared by clinical staging, however, the young patient did as well or better than his older counterpart. Clinical staging was the most important prognostic factor, irrespective of age. No inherent difference was found in the virulence of the cancer in the young, and five-year survival rates were not significantly different in young and old patients (59 percent vs. 49 percent).

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Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin.