CHAPTER 28 Bisphosphonates from A–Z

List of Indications

Indications for which bisphosphonates are already authorised

Osteology

▶ Prevention and treatment of postmenopausal ▶ Prevention and treatment of glucocorticoid-induced osteoporosis ▶ Prevention and treatment of osteoporosis in men ▶ Treatment of Paget’s disease of bone ▶ Prevention of heterotopic ossification

Hematology and Oncology

▶ Hypercalcemia of malignancy ▶ Bone metastases ▶ Osteolyses in multiple myeloma

Clinical Trials have been Successfully Completed, but Bisphosphonates are not yet Officially Authorised for the Following Indications

Osteology, Orthopedic Medicine and Rheumatology

▶ Prevention and treatment of premenopausal osteoporosis ▶ Juvenile osteoporosis ▶ Transplantation osteoporosis ▶ Secondary osteoporoses ▶ ▶ Transient osteoporosis ▶ Bone marrow edema syndrome ▶ Rheumatoid arthritis ▶ Bone pain 222 Chapter 28 Bisphosphonates from A–Z

▶ Renal osteopathy/osteodystrophy ▶ Complex regional pain syndrome (Morbus Sudeck) ▶ Vanishing (Morbus Gorham) ▶ Fibrous dysplasia ▶ SAPHO syndrome ▶ Aseptic loosening of prosthesis ▶ Periodontitis ▶ (e.g., DISH) ▶ Early cases of osteonecroses ▶ Hypercalcemia not associated with malignancy (e.g., inoperable pHPT, sar- coidosis)

Hematology and Oncology

▶ Treatment of osteoblastic bone metastases (e.g. prostatic carcinoma) ▶ Prevention of osteolyses in patients with established bone metastases (e.g. from breast cancer) ▶ Adjuvant therapy for prevention of bone metastases (e.g. from breast cancer) ▶ Prevention of skeletal destruction in multiple myeloma ▶ Antiproliferative therapy in multiple myeloma ▶ Systemic mastocytosis ▶ Bone pain in osteomyelosclerosis ▶ Primary bone tumors and sarcomas with bone metastases

List of Indications in Medical Practice from A–Z

Cardiology Patients on warfarin, long-term therapy Patients on heparin, long-term therapy Chronic heart failure Heart transplantation Dentistry Periodontitis (cave: necrosis of jaw bones) Endocrinology Hyperthyroidism Hyperparathyroidism Diabetes mellitus Cushing’s syndrome Addison’s disease Acromegaly Hypogonadism Klinefelter’s syndrome List of Indications 223

Gastroenterology Primary biliary cirrhosis Chronic hepatitis Hepatic cirrhosis Gastrointestinal operations Crohn’s disease Chronic pancreatitis Malabsorption syndromes Liver transplantation Geriatrics Immobilisation Involutional osteoporosis Gynecology Estrogen deficiency Postmenopausal osteoporosis Metastatic breast cancer Postpartum, after lactation Hysterectomy Bilateral ovariectomy Hematology Multiple myeloma Malignant lymphoma Osteomyelosclerosis Hemolytic anemias Aplastic anemia Systemic mastocytosis Eosinophilic granuloma Histiocytoses Bone pain Myelogenous osteopathies Bone marrow transplantation Infectiology Tuberculosis Leprosy AIDS Malaria Chagas’ disease Leishmaniasis Toxoplasmosis Metabolism Hemochromatosis 224 Chapter 28 Bisphosphonates from A–Z

Oxalosis Hypercalcemia Storage diseases Nephrology Renal osteopathies/osteodystrophies Chronic hemodialysis Renal transplantation Metastatic renal cell carcinoma Hereditary hyperphosphatasia Neurology Antiepileptic drug use Peripheral paresis Systemic myopathies, e.g. multiple sclerosis Diabetic neuropathy Oncology Bone metastases Prevention of metastasis Bone pain Hypercalcemia of malignancy Chemotherapy-induced osteopathy Bone marrow transplantation Osteology/ Osteoporosis syndrome Orthopedics Paget’s disease of bone Gorham’s disease Fibrous dysplasia Aseptic loosening of prosthesis Complex regional pain syndrome Early stage of osteonecrosis DISH (disseminated idiopathic skeletal hyperostosis) Transient osteoporosis (bone marrow edema syndrome) Fatigue fractures Giant cell tumor of bone Immobilisation Osteoarthritis Ankylosing spondylitis Heterotopic calcification List of Indications 225

Fibrodysplasia ossificans progressiva Pediatric Medicine Idiopathic juvenile osteoporosis Osteoporosis of children Immobilisation osteoporosis Osteogenesis imperfecta Storage diseases Inherited collagen disorders Hypercalcemia of children Physical medicine Osteoporosis Immobilisation Arthrosis Psychiatry Anorexia nervosa Depression Antidepressant drug use Pulmonology Bronchial asthma (requiring cortisone) Cystic fibrosis Chronic obstructive pulmonary disorders Sarcoidosis Tuberculosis Metastatic lung cancer Lung transplantation Rheumatology Primary chronic polyarthritis Ankylosing spondylitis Systemic lupus erythematosus Connective tissue diseases Immobilisation Long-term glucocorticoid therapy SAPHO syndrome Space medicine Weightlessness-induced osteoporosis Sports medicine Long-distance running and walking Fatigue fractures Radiation therapy Post-irradiation Surgical trauma- Immobilisation – whole body and regional tology Total endoprosthesis 226 Chapter 28 Bisphosphonates from A–Z

Toxicology Nicotine Alcohol Heavy metals Aluminum Lithium Hydrocarbon poisoning Barbiturates Urology Metastatic prostatic carcinoma Metastatic renal carcinoma

List of Subgroups of Bisphosphonates

Bisphosphonates without Nitrogen

Etidronate Clodronate Tiludronate

Aminobisphosphonates

Pamidronate Alendronate Neridronate

Bisphosphonates with Nitrogen Substitution

Olpadronate Ibandronate

Bisphosphonates with Basic Heterocycles

Risedronate Zoledronate List of Commercial Bisphosphonate Preparations from A to Z 227

List According to Different Modes of Action

Incorporation as ATP-analogues (in ATP containing Compounds): “First-generation” Bisphosphonates

Etidronate Clodronate Tiludronate

Inhibition of the Mevalonate Pathway and Inhibition of Protein Prenylation: “Second-generation” Bisphosphonates: Inhibition of Dimethylallyl-PP

Alendronate Pamidronate

“Third generation” Bisphosphonates: Inhibition of Dimethylally-PP and Geranyl-PP

Risedronate Zoledronate Ibandronate

List of Commercial Bisphosphonate Preparations from A to Z

Trade name Bisphosphonate Application Company Aclasta® Zoledronate I.V. Novartis Actonel® Risedronate Oral Procter & Gamble, Sanofi-Aventis Actonel® 35 mg Risedronate/ Oral Procter & Gamble plus calcium calcium Sanofi-Aventis Aredia® Pamidronate Oral Novartis Bondronat® Ibandronate Oral and I.V. Roche Bonefos® Clodronate Oral and I.V. Medac/Schering Bon(v)iva® Ibandronate Oral and I.V. Roche/GlaxoSmithKline Didronel® Etidronate Oral Procter & Gamble 228 Chapter 28 Bisphosphonates from A–Z

Trade name Bisphosphonate Application Company Didronel-Kit® Etidronate/calcium Oral Procter & Gamble, Aventis Diphos® Etidronate Oral Procter & Gamble Etidronat Etidronate Oral Jenapharm Jenapharm® Fosamax® Alendronate Oral MSD Fosavance® Alendronate/Vit.D Oral MSD Lodronat® Clodronate Oral and I.V. Roche (Austria) Ostac® Clodronate Oral and I.V. Roche Skelid® Tiludronate Oral Sanofi Zometa® Zoledronate I.V. Novartis

List of Authorised Bisphosphonates from A to Z

Bisphosphonate Trade names Alendronate Fosamax®, Fosavance® Clodronate Ostac®, Bonefos® Etidronate Didronel®, Didronel-Kit® Ibandronate Bondronat®, Bon(v)iva® Pamidronate Aredia® Risedronate Actonel®, Actonel® plus calcium Tiludronate Skelid® Zoledronate Zometa®, Aclasta®