Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Preface -- Part I Molecular and cellular environment of bone -- 1 Endochondral bone formation and development in the axial and appendicular skeleton -- Introduction -- The formation of the cartilage anlage in the embryo -- First bone formation -- The growth plates -- The proliferative zone -- The hypertrophic zone: early changes -- Calcification of the hypertrophic zone -- Apoptosis as the end stage of hypertrophic phenotype -- Vascular and chondroclastic erosion of hypertrophic zone -- The formation of woven bone and its replacement with trabecular bone -- The secondary center of ossification -- The regulation of chondrocyte development and chondrocyte interactions with the perichondrium and periosteum -- Vitamin D -- Thyroid hormones -- Estrogen -- Growth hormone (GH) and insulin-like growth factor-I (IGF-I) -- Fibroblast growth factor (FGF) -- Bone morphogenetic proteins (BMPs) -- Hedgehogs, parathyroid hormone (PTH) and PTH related peptide (PTHrP) -- The hedgehog gene family -- Acknowledgements -- REFERENCES -- 2 The role of osteoblasts -- Introduction -- Osteoblast ontogeny -- Mesenchymal stem cells and multipotential and restricted progenitors -- Morphological and histochemical criteria for transitional stages in the differentiation of osteoblasts -- Biochemical and molecular features that characterize differentiation from osteoprogenitor cell to mature osteoblast phenotype -- Progression from the immature progenitor cell to the mature osteoblast and osteocyte: cell culture models -- Cellular features -- Molecular features -- Heterogeneity of the mature osteoblast phenotype -- Osteoprogenitors and osteoblasts in the aging skeleton -- Stage-specific regulation of osteoprogenitor cell differentiation and bone formation -- Acknowledgements -- REFERENCES.

3 Osteoclasts: characteristics and regulation of formation and activity -- Introduction -- Morphological characteristics of osteoclasts -- The mechanism of osteoclastic bone resorption -- The origin of osteoclasts -- Regulation of osteoclast activity and osteoclast differentiation -- REFERENCES -- 4 Bone matrix proteins -- Introduction -- Collagen -- Non-collagenous extracellular matrix proteins -- Bone sialoprotein -- Osteopontin -- Osteonectin/SPARC -- Bone acidic glycoprotein-75 -- Osteocalcin -- Fibronectin -- Small proteoglycans -- Other proteins found in bone matrix -- REFERENCES -- 5 Local regulators of bone turnover -- Introduction -- Insulin-like growth factors -- Fibroblast growth factors -- Transforming growth factor-Beta -- Bone morphogenic proteins -- REFERENCES -- 6 The PTH/PTHrP system and calcium homeostasis -- Introduction -- Overview of calcium homeostasis -- Parathyroid hormone -- Hyperparathyroidism and hypoparathyroidism -- Effect of PTH on bone -- Parathyroid hormone-related protein -- PTH/PTHrP receptor -- PTHrP and PTH/PTHrP receptor in skeletal development -- Haploinsufficient PTHrP mice have skeletal abnormalities -- Targeted overexpression of PTHrP in chondrocytes -- Human chondrodysplasias and PTH/PTHrP receptor mutations -- REFERENCES -- 7 Vitamin D metabolism -- Introduction -- Normal vitamin D physiology -- Vitamin D metabolism -- Vitamin D action -- Action mediated by the nuclear receptor -- VDR polymorphisms -- Non-genomic action of 1,25(OH)2D3 -- Effect of aging on vitamin D status, metabolism and action -- Nutritional and hormonal status -- Vitamin D -- 25OHD -- 1,25(OH)2D -- Vitamin D action -- End-organ responsiveness -- hVDR polymorphisms and bone -- Therapeutic intervention -- Supplementation with D3 -- 1,25(OH)2D3 or 1AlphaOHD3 therapy -- Note added in proof -- REFERENCES.

8 Sodium-dependent phosphate transport in kidney, bone and intestine -- Introduction -- Renal phosphate transport -- Structural identification of renal Na+-phosphate cotransport systems -- Hormonal regulation -- Regulation by dietary phosphate -- Inherited disorders of renal phosphate handling -- Phosphate transport in bone -- Osteoblasts and matrix vesicles -- Osteoclasts -- Intestinal phosphate transport -- REFERENCES -- 9 Molecular genetic analysis of growth factor signaling in bone -- Introduction -- Overview of skeletal development and bone remodeling -- Bone formation -- Bone remodeling -- Conserved signaling pathways in bone -- PTHrP -- FGFR3 -- Gli -- BMPs -- Murine models of disorders of bone metabolism -- History of gene targeting -- The mouse knockout and mutation database -- Targeted disruption of PTHrP and FGFR-3 in mice -- Analysis of compound mutant mouse bones -- Gene therapy in PTHrP+/- neonatal mice -- Acknowledgements -- REFERENCES -- Part II Determinants of peak bone mass -- 10 Genetic determinants of osteoporosis -- Introduction -- Genetics of BMD - a quantitative trait -- The transmission - disequilibrium test (TDT) -- BMD heritability -- Bone turnover heritability -- Genetics of bone fragility -- Candidate genes -- Collagen IA1 -- Vitamin D receptor -- Estrogen receptor alpha -- Transforming growth factor beta -- Other candidate genes -- Genetic syndromes featuring osteoporosis -- Conclusions -- Acknowledgements -- REFERENCES -- 11 Non-genetic determinants of peak bone mass -- Introduction -- Peak bone mass -- Hormonal status and peak bone mass -- Nutrition and peak bone mass -- Acknowledgements -- REFERENCES -- 12 Bone mineral acquisition during childhood and adolescence: physical exercise as a preventative measure -- Introduction -- Normal bone accrual and maintenance -- Bone mineral accrual during growth.

Measurement of bone mineral -- Physical activity and bone -- Does increased activity lead to increased bone mineral accretion? -- Is there a 'window of opportunity' during childhood or adolescence during which bone mineral accretion is optimized? -- Are the benefits of a childhood or adolescent exercise program maintained during adulthood? -- What happens to the skeleton in the absence of physical activity or during mechanical 'unloading'? -- Conclusions -- RECOMMENDED READING -- REFERENCES -- 13 Osteoporosis in children -- Introduction -- Osteogenesis imperfecta -- Clinical presentation -- Family history -- Signs and symptoms -- Clinical classification -- Radiological features -- Laboratory findings -- Differential diagnosis -- Pathophysiology -- Treatment -- Prognosis -- Idiopathic juvenile osteoporosis (IJO) -- Clinical features -- Signs and symptoms -- Radiological features -- Laboratory findings -- Differential diagnosis -- Pathophysiology -- Treatment -- Prognosis -- Secondary osteoporosis -- Corticosteroid-induced osteoporosis -- Immobilization-induced osteoporosis -- REFERENCES -- Part III Pathophysiology of the aging skeleton -- 14 Consequences of alterations in bone remodeling -- The bone remodeling cycle -- Mechanisms of 'uncoupling' -- The pathogenesis of osteoporosis -- Sex hormones -- Other hormones regulating bone turnover -- Local factors in osteoporosis -- Cytokines -- Prostaglandins -- Growth factors -- Conclusion -- REFERENCES -- 15 The role of parathyroid hormone and hyperparathyroidism in osteoporosis -- Introduction -- Indirect evidence for a permissive role of parathyroid hormone in osteoporosis -- Role of parathyroid hormone in osteoporosis -- Role of PTH in primary osteoporosis -- Role of menopause in type I osteoporosis -- Aging, secondary hyperparathyroidism and type II osteoporosis -- Role of PTH in secondary osteoporosis.

Primary hyperparathyroidism (PHP) -- Secondary hyperparathyroidism (SHP) -- Gastrointestinal diseases -- Renal failure -- Conclusion -- PTH inhibition in the treatment of osteoporosis -- REFERENCES -- 16 Senile Osteoporosis -- Introduction -- Patterns of bone loss over time -- Mechanisms of bone loss in women -- Accelerated, transient phase of bone loss -- Slow, protracted phase of bone loss -- Mechanisms of bone loss in men -- Conclusion -- REFERENCES -- Part IV Clinical aspects of osteoporosis -- 17 Biochemical markers of bone turnover -- Biochemical markers of bone resorption -- Collagen cross-link markers: pyridinolines and telopeptides (urine or serum) -- Hydroxyproline and hydroxylysine glycosides -- Urinary calcium-to-creatinine ratio -- Tartrate-resistant acid phosphatase (TRAP) -- Biochemical markers of bone formation -- Alkaline phosphatase - total and bone specific -- Osteocalcin -- Serum procollagen extension peptides -- Use of biochemical markers in metabolic bone disease -- Paget's disease of bone -- Malignant bone disease -- Osteomalacia -- Hyperthyroidism -- Hyperparathyroidism -- Osteoporosis -- Conclusions -- REFERENCES -- 18 Radiologic assessment of osteoporosis -- Introduction -- Quantification of osteoporosis -- Plain radiography and osteoporosis -- Osteopenia -- Differential diagnosis of osteoporosis -- REFERENCES -- 19 Bone mineral density measurements -- Diagnosis of osteoporosis using bone densitometry: the WHO criteria -- Why are bone mass measurements performed? -- The diagnosis of osteopenia and osteoporosis -- The prediction of fracture risk -- Serial assessments of bone mass -- Conclusions -- REFERENCES -- 20 Hormone replacement therapy -- Effects of hormone replacement therapy on bone -- Cellular effects -- The effects of HRT on bone mineral density -- HRT and vertebral fractures -- HRT and hip fractures.

Effects of hormone replacement therapy on other systems.