Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate

Ochronosis as an unusual cause of a valvular defect: a case report

INTRODUCTION: Alkaptonuria (also known as ochronosis) is a genetic disorder characterised by the accumulation of homogentisic acid deposits in connective tissue. In rare cases, ochronosis can cause valvular heart disease. CASE PRESENTATION: We present the case of a 68-year-old Caucasian man with alkaptonuria-associated degenerative valvular defects with aortic, mitral and tricuspid valve insufficiency. The patient did not have any cardiac complaints and was referred to our clinic for evaluation of a conspicuous new heart murmur. CONCLUSION: This case report shows that early diagnosis of cardiovascular ochronosis gives us the opportunity to use conservative treatment to slow down the progression of valvular dysfunction