To describe an elderly patient with low serum alkaline phosphatase (ALP) activity detected after a pathologic fracture and to characterize hypophosphatasia in adult patients.
We present a case report of a 64-year-old woman, who was referred after sustaining an atraumatic femoral fracture treated successfully with intramedullary nailing. Clinical, biochemical, radiologic, and molecular studies explore the differential diagnosis of her hypophosphatasemia, and the features, diagnosis, and management of the adult form of hypophosphatasia are reviewed.
Physical examination of our patient was revealing only for short stature. Bone mineral density evaluated by dual-energy x-ray absorptiometry was unremarkable. Biochemical investigations showed normal calcium, elevated inorganic phosphate, and low ALP levels in serum. In light of the hypophosphatasemia and pathologic fracture, the serum pyridoxal 5'-phosphate concentration was measured and found to be considerably elevated, a substantiation of the diagnosis of hypophosphatasia. Analysis of the gene encoding the "tissue-nonspecific" isoenzyme of ALP (TNSALP) demonstrated a novel, heterozygous, missense mutation causing her disorder.
Hypophosphatasia is a rare inborn error of metabolism due to a deactivating mutation (or mutations) of the gene encoding TNSALP, in turn leading to global deficiency of TNSALP activity and inadequate skeletal mineralization and fractures. Our patient illustrates the importance of low serum ALP activity in the assessment of patients with fractures. No established treatment exists for hypophosphatasia, but the correct diagnosis should help to avoid the use of traditional therapies for osteoporosis or osteomalacia, which would be ineffective or potentially harmful.
[Show abstract][Hide abstract] ABSTRACT: Biomaterials are widely used in medical practice to help maintain, improve or restore diseased tissues or organs. The successful integration of biomaterials with host tissue depends on substratum surface properties, as well as host tissue quality and its regulatory environment. The overall goal of this dissertation is to incorporate these three factors to achieve better biomaterial-host tissue interactions. Important surface properties include surface topography, surface energy, chemical composition and surface charge. We designed a new titanium (Ti) substratum with modified surface chemical composition by preventing the contamination when in contact with the atmosphere. The new Ti surface has lower carbon contamination and promotes osteoblast differentiation phenotype. The osteogenic effect is synergistic with micrometer and sub-micrometer scale surface structures. To further investigate the effects of bone quality on peri-implant bone formation, we developed a novel mouse femoral medullary bone formation model. This new model will facilitate research evaluating the effects of biomaterial surface treatments in host animals with deficient bone development, including genetically engineered mice. Finally, we studied sexual dimorphism in the response of osteoblasts to systemic regulatory hormones 1¦Á,25-dihydroxyvitamin D3 and 17¦Â-estradiol. The results showed intrinsic differences in male and female osteoblasts with respect to their differentiation and their responses to hormones, suggesting that host chromosomal sex should be considered in biomaterial research. Taken together, this research provides fundamental information on biomaterial surface properties and the regulation of host tissue response, which are important in guiding biomaterial design and evaluation. Ph.D. Committee Chair: Barbara Boyan; Committee Co-Chair: Zvi Schwartz; Committee Member: Andres Garcia; Committee Member: Carson Meredith; Committee Member: Robert Baier
[Show abstract][Hide abstract] ABSTRACT: Hypophosphatasia is an inheritable disorder characterised by defective bone mineralisation due to the impaired activity of tissue-non-specific alkaline phosphatase (AP). Clinical presentation ranges from stillbirth without mineralised bone to pathological fractures in late adulthood. During childhood, the main manifestations include rickets, growth delay and dental problems. Fractures and bone pain usually characterise the adult form. A 9-year-old girl was referred for repetitive fractures after minimal trauma. She had normal growth, normal sclerae, no rickets and minimal dental abnormalities. Her sister had also presented fractures. The proband, her sister and mother had low total and bone-specific AP levels and E435K mutation in exon 12 of the liver/bone/kidney AP gene. Low AP levels must lead to genetic analysis. Bone fragility and repetitive fractures may be symptoms of hypophosphatasia in childhood, which must not be neglected. Associated factors such as vitamin D or calcium deficiency must be prevented. In conclusion, hypophosphatasia must not be forgotten as an aetiological factor of repetitive fractures or bone pain in children and AP activity should be checked accurately.
European Journal of Pediatrics 10/2008; 168(7):783-8. DOI:10.1007/s00431-008-0835-6 · 1.89 Impact Factor
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