Oral bisphosphonate alendronate does noot reduce the incidence of fractures in children with osteogenesis imperfecta. This has been suggested by findings findings published November 24th online in The Journal of Clinical Endocrinology & Metabolism.

With an objective  to study the efficacy and safety of daily oral alendronate  in children with osteogenesis imperfecta, Dr Ward et al conducted a multicenter, double-blind, randomized, placebo-controlled study.

The study included 139 children between  4–19 years of age having  with type I, III, or IV osteogenesis imperfecta.

They found that as compared to placebo, alendronate increases spine bone mineral density but long-bone fracture incidence, average midline vertebral height, iliac cortical width, bone pain, and physical activity were similar between groups. Bone turnover also decreased to a greater extent with alendronate.

The incidences of clinical and laboratory adverse experiences were also similar between the treatment and placebo groups.

The authors concluded that oral alendronate  for 2 years in pediatric patients with osteogenesis imperfecta significantly decreased bone turnover and increased spine areal bone mineral density but was not associated with improved fracture outcomes.

J Clin Endocrinol Metab    published November 24, 2010 as doi:10.1210/jc.2010-0636

Related posts:

1. Strontium Ranelate May Reduce Backpain In Osteoarthritis of spine
2. Nutrient Rich Diet May Reduce Risk Of Low Trauma Fracture
3. Helmets Reduce Risk of Head Injury In Skiers and Snowboarders

The study included 89 patients who were put on infiximab and it was found that found obese patients improved less than leaner ones.

The study has been published in online November 8th in Arthritis & Rheumatism,

It is not clear why does this occur but  adipocytokines — inflammation-promoting proteins produced by fat tissue  are thought to play a role.

This may send an alert to the physicians that TNF blockers might be relatively less effective in obese people.

Related posts:

1. Xray of Bilateral Hands In Rheumatoid Arthritis Showing Dislocation of All Metacarpophalangeal Joints
2. Tocilizumab Inhibits Joint Damage In Rheumatoid Arthritis Not Adequately Controlled With Methotrexate
3. Orthotics May Relieve Pain Around Ankle and Foot In Rheumatoid Arthritis

The drug has already been approved and in market for postmenopausal osteoporosis.

The drug is used in different doses in in these two conditions.

The drug is administered subcutaneously.

In cancer patients with bone metastases, to prevent skeletal complications, the dosage is 120 mg every 4 weeks. For postmenopausal osteoporosis, it is administered at a dose of 60 mg every 6 months.

The novel drug is a fully human monoclonal antibody that binds to RANK ligand, a protein found on osteoclasts and involved in bone breakdown.

According to three trials the drug has shown superiority over bisphosphnates in prevention of skeletal events in cancer patients.

Denosumab has been launched as XGEVA by Amgen, who had funded all the trials

Related posts:

1. Zoledronic Acid Increases Survival In Addition To Prevention Of Skeletal Events In Multiple Myeloma
2. Oral Bisphosphonates May Cause Esophageal Cancer
3. New Drug Humira Approved By USFDA For Treatment Of Juvenile Arthritis

That gives many of the chronic pain patients another treatment option.

Duloxetine has been approved for both chronic low back pain and osteoarthritis. The decision was based on data from 4 double-blind, randomized clinical trials.

The recommended dose is 60 mg daily.

Nausea, dry mouth, insomnia, sleepiness, constipation, dizziness, and fatigue are most commonly reported adverse effects.

Serious adverse effects occur in less than 1% of patients and include hepatotoxicity, allergic/hypersensitivity reactions, pneumonia, and suicidality.

Previously, duloxetine has been approved for use in the treatment of major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, and fibromyalgia.

Related posts:

1. FDA Approves Adaptive Neurostimulation Device – Medtronic AdaptiveStim with RestoreSensor
2. Aquatic Relief For Chronic Pain of Fibromyalgia
3. Topical NSAIDs Safe, Effective for Acute Musculoskeletal Conditions

The review was initiated with a goal to assess the efficacy of vitamin D supplementation for improving bone mineral density in childre

Related posts:

1. Myasthenia Gravis In Children
2. Neuropathic Joint Disease or Charcot Joint in Children
3. Bacterial Infections of Spine In Children

Following are  second-line drugs used for the treatment of tuberculosis.

• Thioacetazone (T)
• P-aminosalicylic acid (PAS or P).
• Thioamides – Ethionamide, prothionamide
• Cycloserine
• Polypeptides- capreomycin, viomycin, enviomycin
• Aminoglycosides: e.g., amikacin (AMK), kanamycin (KM)
• Fluoroquinolones-Ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF), Ofloxacilin

Commonly used drugs are discussed below-

Thiacetazone

Thioacetazone is a bacteriostatic drug [Inhibits the growth of bacteria but does not kill existing]. It  has poor cerebrospinal fluid penetration. Its mechanism of action is not clear. The dose of the drug is 150 mg per oral. It may cause gastrointenstinal  disturbances, skin reactions including exfoliative dermatitis,hepatotoxicity, myelosuppression [suppression of bone marrow].

It is not used in AIDS patients. Due to its toxic profile the use of Thioacetazone is reducing and it is used in cases where other choices have exhausted.

PAS

P-aminosalicylic acid is again a bacteriostatic drug with poor CSF penetration. It acts by inhibiting folate synthesis and interferes with incorporation of p-amino benzoic acid. The dose is 150 mg/kg per oral in divided doses with meals. Maximum allowed dose is 12 gm.

Side effects like gastrointenstinal disturbances, hypersensitivity like rash, feve malaise, arthralgia,  and  changes in blood count like leucopenia, agranulocytosis, eosinophilia, lymphocytosis, atypical mononucleosis, thrombocytopenia, hemolytic anemia. This drug is active against mycobacterium tuberculosis only.

Ethionamide

It is a bacteriostatic drug  and has a good CSF penetration.  It acts as nicotinamide analog and possibly inhibits incorporation of cysteine and methionine proteins. It is recommended in doses of 15-20 mg/kg orally in divided doses with meals.  The maximum dose should not increase more than one gram.

The known side effects are gastrointenstinal  disturbances, neurotoxicity, visual disturbances, olfactiry distubances, peripheral neuropathy, convulsions, hepatotoxicity, hypersensitivity reactions, alopecia and gynecomastia.

Pyridoxine supplements can reduce the toxicity. Liver functions must be monitored during therapy.

If used alone, resistance develops very soon. It also shows cross resistance with thioacetazone

Cycloserine

A bacteriostatic drug with very good CSF penetration. It inhibits cell wall synthesis. Dose is 10-20 mg/kg per oral in 2 divided doses. Maximum dose is 500 mg twice daily. Headcahe, dizziness, vertigo, drowsiness, tremors, convulsions, depresion, psychosis, abnormal liver function, megaloblastic anemia, rashes are known side effects.

Hematological, renal and hepatic functions should be monitored.

Capreomycin

The drug is given in intramuscular injection form. It is a bacteriocidal drug with poor CSF penetration. The dose is 15-30mg/kg . Maximum dose is 1 gram. Induration at the site of injection, Ear and kidney toxicity, fever, rashes, eosinophilia are known side effects. High doses may cause neuromuscular blockade. Resistance  to this drug develops after short use. It also shows cross resistance with aminoglycosides.

Amikacin, Kanamicin

These are bacteriocidal drugs that belong to aminoglycocide class and have poor CSF penetration. Dose is 15mg/kg intramuscular injection form.

Ootoxicity, nephrotoxicity, pesudomembranous colitis and neuromucular blockade are common side effects.

Fluoroquinolones should not be used in children.

Newer drugs like macrolides (e.g. Azithromycin; Clarithromycin), rifamycins, (e.g. Rifabutin and the long-acting Rifapentine) and nitroimidazoles (e.g. PA-824) are being evaluated fro their efficacy.

Related posts:

1. Toxicity of Antitubercular Drugs
2. First Line Drugs For Tuberculosis
3. First Line Drugs For Tuberculosis Treatment – Recommended Doses

• Isoniazid
• Rifampin
• Pyrazinamide
• Ethambutol
• Streptomycin

These five drugs are responsible for control and containment of tubercular disease, among other factors.

The drugs are given on basis of patient weight and dosage may vary in different individuals. The dosage also differ depending on the regimen given. There are three regimen that traditionally have been used for treatment

• Daily
• Twice Weekly
• Thrice Weekly

Dosage In Children

Daily Regimen

Isoniazid 10-20 mg/kg
Rifampin 10-20 mg/kg
Pyrazinamide 15-30 mg/kg
Ethambutol 15-25 mg/kg
Streptomycin 20-40 mg/kg

Twice Weekly Regimen

Isoniazid 20-40 mg/kg
Rifampin 10-20 mg/kg
Pyrazinamide 50-70 mg/kg
Ethambutol  50 mg/kg
Streptomycin 25-30 mg/kg

Thrice Weekly Regimen

Isoniazid 20-40 mg/kg
Rifampin 10-20 mg/kg
Pyrazinamide 50-70 mg/kg
Ethambutol 25-30 mg/kg
Streptomycin 25-30 mg/kg

Dosage In Adults

Daily Regimen

Isoniazid 5 mg/kg
Rifampin 10 mg/kg
Pyrazinamide 15-30 mg/kg
Ethambutol  15-25 mg/kg
Streptomycin 12-18 mg/kg

Twice Weekly Regimen

Isoniazid 5 mg/kg
Rifampin 10 mg/kg
Pyrazinamide 50-70 mg/kg
Ethambutol  50  mg/kg
Streptomycin 25-30 mg/kg

Daily Regimen

Isoniazid 15 mg/kg
Rifampin 10 mg/kg
Pyrazinamide 50-70 mg/kg
Ethambutol  25-30 mg/kg
Streptomycin 25-30 mg/kg

Note

• Doses based on weight must be adjusted as the patient’s weight changes
• Pyrazinamide and streptomycin should not be used to treat pregnant women.
• Ethambutol is not recommended for children who are too young to be monitored for changes in their vision.
• Daily dose of streptomycin should not exceed 0.75 g for patients over 50 years of age.

The World Health Organization does not recommend twice weekly regimens because of the greater risk of treatment failure from missed doses.

Related posts:

1. First Line Drugs For Tuberculosis
2. Toxicity of Antitubercular Drugs
3. Second Line Antitubercular Drugs

Calcitonin is the hypocalcaemic hormone discovered by Copp in 1962. It is a 32 amino acid single polypeptide produced by parafollicular ‘C’ cells of thyroid. Parathyroids, thymus and cells of medullary carcinoma of thyroid also contain calcitonin.

Synthesis and secretion of calcitonin is regulated by calcium concentration itself. Rise in plasma calcium increases while fall in plasma calcium decreases calcitonin release.

The actions of calcitonin are generally opposite to that of parathyroid hormone. It inhibits bone resorption by direct action on osteoclasts-decreasing their ruffled surface which forms contact with the resorptive pit. It is doubtful whether it also promotes calcium deposition by osteoblasts. The hypocalcemic action of calcitonin lasts ~8 hours.Calcitonin inhibits proximal tubular calcium and phosphate reabsorption by direct action on kidney. However, hypocalcaemia which occurs overrides the direct action by decreasing the total calcium filtered filtered at the glomerulus urinary calcium is actually reduced.

The actions of calcitonin are probably mediated through increase in cAMP formation, but its target cells are different from that of PTH.

Synthetic salmon calcitoin is used clinically, because it is more potent due to slower metabolism. Human calcitonin has also been produced.

Adverse effects experienced are nausea, flushing, tingling of fingers, bad taste and allergic reaction. By lowering plasma calcium calcitonin may interfere with action of digoxin.

Uses

Hypercalcaemic States

Hyperparathyroidism, hyper vitaminosis D, osteolytic bony metastasis. It acts rapidly, but refractoriness develops over time and other measures to reduce plasma calcium are more convenient.

Postmenopausal Osteoporosis

100 IU s.c. or i.m. daily along with calcium and vitamin D supplements.

A nasal spray formulation delivering 200 IU per actuation has become available. One spray in one nostril daily has been shown to increase bone mineral density in menopausal women effect becoming perceptible after 6 months therapy; and maintained thereafter. It is indicated when estrogens cannot be given and the women is menopausal for at least 5 years with definite evidence of osteoporosis. Rhinitis, epistaxis, nasal ulceration and headache are side effects.

Paget’s Disease

100 U daily or on alternate days produces improvement for view months. Later, resistance usually develops due to production of antibodies. Human calcitonin may prove better in this regard.

Related posts:

1. An Overview of Calcium and Its Role In Body Metabolism
2. An Overview of Parathyroid Hormone

Parathormone is stored in intracellular vesicles after its synthesis. Secretion of PTH is regulated by plasma Calcium concentration. Fall in plasma calcium induces parathormone release and rise inhibits secretion.

Changes in phosphate concentration in plasma affect parathormone secretion indirectly by altering Calcium concentration.

Parthyroid Hormone increases plasma calcium levels by increasing resorption of calcium from bone and decreasing the excretion of calcium in urine. It also promotes phosphate excretion which tends to supplement the hypercalcaemic effect.

Mechanism of action

The parathormone receptor is a G protein coupled receptor which on activation increases cAMP formation and intracellular Ca2+ in target cells. In bone the target cell appears to be the osteoblast because parathormone receptors are not expressed on the surface of osteoclasts.

It has been proposed that parathormone osteoblast complex somehow increases the activity of osteoclasts.

Hyperparathroidism

With increased levels of parathyroid hormone low plasma calcium level may result. This may lead to following

• Low plasma calcium levels
• Tetany
• Convulsions
• Laryngospasm
• Paresthesias
• Cataract
• Psychiatric changes.

Symptoms of hyperparathyriodism are Hypercalcaemia, decalcification of bone – deformities and fractures, metastatic calcification, renal stones, muscle weakness, constipation and anorexia.

Treatment is surgical removal of the parathyroid tumour.

Related posts:

1. An Overview of Calcium and Its Role In Body Metabolism
2. Calcitonin

After C,H,O and N, Calcium is the most abundant body constituent, making up about 2 percent of body weihgt: 1-5 kg in an adult. Over 99% of this is stored in bones, the rest being distributed in plasma and all tissues and cells.

Physiological Roles

1 Calcium controls excitability of nerves and muscle and regulates permeability of cell membranes. It also maintains integrity of cell membranes and regulates cell adhesions.

2 Ca2+ ions are essential for excitation contraction coupling in all types of muscle and excitation secretion coupling in exocrine and endocrine glands, release of transmitters from nerve ending and other release reactions.

3 Intracellular messenger for hormones, autacoids and transmitters.

4 Impulse generation in heart determines level of automaticity and A-V conduction.

5 Coagulation of blood.

Plasma Calcium Level

Plasma Calcium Level is precisely regulated by 3 hormones almost exclusively devoted to this function

• Parathormone (PTH)
• Calcitonin
• Calcitriol (active form of vitamin D).

Normal plasma calcium is 9-11 mg/dl.

40 percent is bound to plasma proteins-chiefly albumin; 10 percent is complexed with citrate, phosphate and carbonate in an undissociable form; the remaining (about 50 percent) is ionized and physiologically important.

Acidosis favours and alkalosis disfavours ionization of calcium: hyperventilation precipitates tetany and laryngospasm in calcium deficiency by reducing ionization.

Absorption and Excretion

Calcium is absorbed by facilitated diffusion from the entire small intestine as well as from duodenum by a carrier mediated active transport under the influence of vitamin D.

Phytates, phosphates, oxalates and tetracyclines and interfere with absorption.

Glucocorticoids and phenytoin also reduce calcium absorption.

All ionized calcium is filtered at glomerulus and most of it is reabsorbed in the tubules. Vitamin D increases and calcitonin decreases proximal tubular reabsorption, while parathormone increases distal tubular reabsorption of Ca2+. About 300 mg of endogenous calcium is excreted daily: half in urine and half in faeces.

To maintain calcium balance the same amount has to be absorbed in the small intenstine from diet. Because normally only 1/3 of ingested calcium is absorbed, the dietary allowance for calcium is 0.8-1.5 g per day. However, calcium deficiency and low dietary calcium increases fractional calcium absorption.

Thiazide diuretics impede calcium excretion by facilitating tubular reabsorption.

Side Effects

Calcium supplements are usually well tolerated; only gastrointenstinal side effects like constipation, bloating have been reported.

Related posts:

1. An Overview of Parathyroid Hormone
2. Calcitonin
3. Vitamin D Supplements Do Not Benefit Healthy Children