Module locomotor system

Clinical case

A 35 years old Afghani female presented with history of bone pains throughout the body for last 3 months, she had also difficulty in climbing stairs and her family members have noticed that she was not properly walking as before. She has 6 children, and lactating her last child of one year old. On examination she is anaemic , tenderness on long bones and proximal muscle weakness.

Investigations revealed serum ca 7mg/dl, serum albumin 4 mg/dl , serum phosphate2mg/dl, alkaline phosphatase 1046U/l.

The following x-rays were performed.

Questions ;

  1. Why the patient is having pain in all bones of the body?
  1. Why is she having difficulty in climbing stairs?
  1. What is this disease known as?
  1. What abnormality must have the family members noticed about her walking?
  1. Does her disease to do anything with her number of children and lactation?
  1. What is the daily requirement of calcium in normal adult?
  1. What are the factors for decrease calcium in this patient?
  1. What is meant by proximal muscle weakness?
  1. What is meant by corrected calcium level and how is it calculated?
  1. What is the reason for raised alkaline phosphatase?
  1. What abnormality is seen in the x-rays?
  1. What happens to shape of pelvis?
  1. Why the bones get deformed?
  1. What is the normal components of bone?
  1. What are the natural products rich in calcium?
  1. What is the normal vitamin D requirement?
  1. What is the treatment of her disease?
  1. what are the natural sources of vitamin D?
  1. What is the response of treatment?
  1. What is the difference between rickets and osteomalacia?
  1. Other than decrease intake, increase demand and sunlight other factors leading to decrease calcium?
  1. How would the parathyroid hormone respond to decrease calcium and phosphate?

Facilitators guide

Osteomalacia

It is the adult counterpart of rickets and occurs after the growth plate have fused.it is a metabolic bone disease with decrease mineralization of the bone matrix(osteoid).

ACTIVATION OF VITAMIN D

Pathogenesis of osteomalacia

The most common cause of osteomalacia is a deficiency of vitamin D. Vitamin D insufficiency can cause osteomalacia because vitamin D facilitates calcium absorption and other minerals in the gastrointestinal tract necessary for bone building. Lack of vitamin D, calcium and other minerals aren’t absorbed efficiently, so they are not available for mineralization in the bone building process. This then result in soft bones. In the bones there will be increase in the fraction of the forming surface covered by incompletely mineralized osteoid, an increase in osteoid volume and thickness and a decrease in the calcification .

Normal

Osteomalacia

Physiological Role of Calcium

•Maintain the integrity of the skeleton:

–Calcium phosphate – incorporated into bone and teeth

•Control of biochemical processes:

–Intracellular:

•Activity of a large number of enzymes

•Conveying information from the surface to the interior of the cell (2nd messenger)

–Extracellular:

•Muscle contraction and nerve function (neurotransmitter release into synapse)

•Blood clotting (cofactor for enzymes involved in blood clotting)

–Release of peptide/amine hormones from endocrine cells

•The biochemical role of Calcium requires that its blood plasma concentrations be precisely controlled

•Normal concentration of about 9 mg/dl must be maintained within small tolerances despite

–variations in dietary calcium levels

–variation in demand for calcium

•Humans and other mammals have an effective feedback mechanism for regulating plasma concentration of calcium [Ca]p

Calcium in the Body

•99% body calcium in skeleton

•0.9 % intracellular

•0.1% extracellular

•Exists in free and bound states, 50% bound

–Albumin (40% total calcium)

–Phosphate and citrate (10% total calcium)

Major sites of Calcium regulation

The hormones that regulate calcium homeostasis

•Parathyroid hormone (PTH) secreted in response to low blood calcium concentration. Increases calcium by:

  1. Stimulating renal conversion of 25-(OH)D3 to 1,25-(OH)2D which increases intestinal Ca++ absorption.
  2. Directly stimulates renal Ca++ absorption and PO43- excretion.
  3. Stimulates osteoclastic resorption of bone

•1,25(OH)2D (vitamin D metabolite) –

  1. Increases GI absorption of dietary Ca++
  2. Stimulates both osteoblast and osteoclast activity according to the concentration of Ca in the blood
  3. Mineralization of bone

•Calcitonin secreted in response to high calcium in blood

  1. Inhibit osteoclastic resorption of bone
  2. Increases renal Ca++ and PO43- excretion

Feedback mechanism that controls calcium homeostasis

•Four organs

  1. the parathyroid glands,
  2. intestine,
  3. kidney,
  4. and bone

together determine the parameters of calcium homeostasis.

•+, positive effect; -, negative effect; 1,25 D, 1,25-dihydroxy vitamin D; ECF, extracellular fluid; PTH, parathyroid hormone.

Causes and risk factors for osteomalacia

•Insufficient sunlight exposure Sunlight makes vitamin D in your skin. Therefore osteomalacia can develop in people who spend little time in the sunlight, wear very strong sunscreen, live in areas where sunlight hours are short, or where the air is smoggy.

•Insufficient vitamin D intake A diet low in vitamin D is the most common cause seen worldwide. Is less common in the U.S. because many foods, such as milk and cereals are fortified with vitamin D.

•Certain Surgeries The removal of part or all of your stomach known as gastrectomy, can lead to this disease because the stomach breaks down foods to release vitamin D and other materials, which are then absorbed by your intestines. Surgery removing or bypassing your small intestine can lead to osteomalacia.

•Chronic pancreatitis Pancreatitis is the long-standing inflammation of your pancreas, an organ that makes digestive enzymes and hormones. If the pancreas is inflamed enzymes in charge of breaking down food and releasing nutrients do not flow as freely into your intestines.

•Chronic sprue In this autoimmune disorder, the lining of the small intestine is damaged by consuming foods having gluten, a protein found in wheat, barley, and rye. Damaged intestinal lining doesn’t absorb nutrients, such as vitamin D, as well as a healthy one would.

Symptoms/Diagnosis

In the early stages of osteomalacia a person may not feel the symptoms, but may be seen in x-rays or diagnostic tests. As osteomalacia worsens symptoms may include bone pain and muscle weakness. Bone pain is especially felt in the lower spine, pelvis, legs and feet. The pain is dull and aching and get worse with physical activity. Even gentle pressure on the bone may cause severe pain.

Osteomalacia may cause weakness and stiffness in the arms and legs, decreased muscle tone and discomfort during movement. Some people also walk with a waddling motion.

When diagnosing osteomalacia, doctors will inquire about the patient’s time spent in the sun and about their diet. In order to rule out other bone diseases the following tests may be conducted:

Blood and urine tests In the cases caused by vitamin D deficiency or phosphorous loss, abnormal levels of vitamin D and minerals calcium and phosphorous are often detected through blood and urine tests.

X-ray Slight cracks in the bones which are visible on x-rays known as looser transformation zones are characteristic of people with osteomalacia ·Bone scan Bone scans detect areas of high and low bone metabolism in your body. Radioactive dye is injected in the vein and a picture of the amount of radioactive dye gathers in your bones. Those with osteomalacia have radioactive dye unevenly distributed in some areas of their bones.

Bone biopsy A bone biopsy is performed by inserting a slender needle through the skin and into the bone to withdraw a small sample, which is then viewed under a microscope. Even though bone biopsies are very accurate in detecting osteomalacia, it is often not needed to make the diagnosis.

Treatment

When osteomalacia is caused from a dietary or sunlight deficiency, replenishing the low levels of vitamin D in the body usually cures the condition. Doctors also recommend vitamin D supplements depending on the dose needed and whether you have other health problems. Most people with osteomalacia take vitamin D supplements by mouth for several weeks or months. Although uncommon, vitamin D can also be given as an injection or through a vein in the arm.

 If the blood levels of calcium and phosphorous are low the patient may also take supplements of these minerals.

 After a patient begins treatment, they may undergo periodic blood tests to assure blood levels of vitamin D and certain minerals are within normal limits. X-rays are also taken to determine the improvement of the bones. Symptoms may lessen within a few weeks of treatment. Doctors suggest that patients continue taking vitamin D indefinitely to prevent the return of osteomalacia

Prevention

Osteomalacia caused by inadequate sun exposure and a diet low in vitamin D can be prevented.

Spend a few minutes in the sun Direct exposure in the sun to the arms and legs for five to ten minutes daily is sufficient for adequate vitamin D production. If a person lives in cold climate and don’t get enough sun exposure during the winter, they can build enough vitamin D stores in the skin during warmer months. Although regular use of sunscreen helps prevent skin cancer and premature aging of the skin, there is concern that the frequent use of strong sunscreen can increase the risk of developing ostemalacia.

Eat food high in vitamin D Eat foods that are naturally rich in vitamin D such as oily fishes (salmon, mackerel, and sardines) and egg yolks. Other foods that are fortified with vitamin D include cereal, bread, milk, and yogurt.

Take supplements If a person doesn’t get enough vitamins and minerals in their diet or if they have a medical condition affecting the ability of their digestive system to absorbing nutrients, they are recommended to ask a doctor about taking vitamin D and calcium supplements.

Exercise Exercise such as walking helps strengthen bones, but if a patient has slight fractures due to osteomalacia, they should avoid strenuous activity until their bones heal.

Key for questions.

1.Decrease calcium and phosphate results in decrease bone mineralization of bones so they become weak and also cannot bear the stress which leads to pain.

2 Pelvic muscles become weak so the patient has difficulty in climbing stairs and difficulty in getting up from squatting posture.

3. This disease is known as osteomalacia

4.Patients have typical waddling gait like a duck in moderate to severe osteomalacia.

5.Yes, there is an increase demand of calium during pregnancy and lactation as most of the mothers calcium is utilized by the foetal bones and formation of milk.so if proper requirement are not fulfilled it leads to deficient state.

6.Daily requirement of calcium is 1000 mg / day

7.Factors for decrease calcium are increase demand during pregnancy and lactation and also she is an afghani who are strict purda observing so their skin not exposed to sunlight to activate vitamin D which is an important vitamin to maintain calcium balance.

8.Proximal muscles mean pelvic and pectoral group of muscles.

9.Calcium in the body is either free or ionized form or bound to albumin. Corrected calcium is the ionized or free calcium in blood and is calculated by adding 1 mg/ dl to serum calcium for every g/dl that serum albumin is below 4 g/dl

10. Increase osteoblastic activity leads to increase alkaline phosphatase.

11, There are pseudofractures or loozers zone which are formed on sites where vessels cross the bones and its pulsations cause shear stress on those sites of bones .commonly found around femoral neck ,medial border of scapula,upper fibula,pelvis.

12. Pelvic bone becomes heart shaped or triradiate.

13.As the bones are not mineralized ,so are soft and so cannot maintain their normal shape and integrity.

14.Normal bone composition is

•The matrix

–40% organic

•Type 1 collagen (tensile strength)

•Proteoglycans (compressive strength)

•Osteocalcin/Osteonectin

•Growth factors/Cytokines/Osteoid

–60% inorganic

•Calcium hydroxyapatite

•The cells

–osteo-clast/blast/cyte/progenitor

15. Natural sourse of calcium are milk, yogurt,eggwhite.

16.Normal vitamin D requirement is 400 IU/day

17. Replacement of calcium and vitamin D

18. Natural sources of vitamin D is sunlight, oily fishes (salmon, mackerel, and sardines) and egg yolks. Other foods that are fortified with vitamin D include cereal, bread, milk, and yogurt.

19. With treatment gradually pain subsides and also patients develop power in girdle muscles.calcium levels improve and alkaline phosphatase decrease.

20.In rickets the growing skeleton is involved, defective mineralization occurs in bone and cartilaginous matrix of growth plate. Whereas osteomalacia occurs in adults due decrease mineralization of bones when the epiphyseal growth plates have closed.

21.Other causes for osteomalacia are chronic pancreatitis, malabsorption syndromes,stomach and intestinal surgeries and renal diseases.

22. Decrease calcium results in increase in paratharmone levels.