POSTMENOPAUSAL OSTEOPOROSIS

POSTMENOPAUSAL OSTEOPOROSIS (PRIMARY TYPE 1 OSTEOPOROSIS)

---

(ARTICLE BY: Hina Fatima, 3rd Year MBBS, Rawalpindi Medical College)

The term osteoporosis as defined by The National Institutes of Health Consensus Conference reveals “a disease of increased skeletal fragility accompanied by a low bone mineral density (a T score for bone mineral density lower than 2.5) and microarchitectural deterioration”.
Postmenopausal osteoporosis,however strongly refers to women beyond their age of menopause (late 40’s or early 50’s)  and may range from asymptomatic bone loss to debiliating hip fractures.

Pathogenesis

Referring specifically to our case,in pathogenesis we come across a hormonal factor which strongly affects one of the three mehanisms (inadequate peak bone mass, excessive bone resorption, inadequate formation of new bone during remodeling) involved in development of osteoporosis “excessive bone resorption”-and the hormone being “Estrogen” which is diminuted after a woman enters her menopause. Estrogen puts a restraint on Bone remodeling cycles but with the  loss of this restraint the frequency of activation of remodeling cycles is increased with a subsequent increase in bone resorption and formation. Osteoclasts are increased in number in trabecular bone as their apoptosis is delayed at the end of resorption and this results in large resorption  cavities  filled only partialy by the osteoblastic activity.there is also simultaneous remodeling on opposite side of these trabeculae leading to complete transection of trabeculae and loss of the platform on which new bone had to be laid down.
Estrogen acts on bones

• directly via a receptor mediated action on osteoblast-like cells and increases levels of pro-collagen type 1 and TGF-β m-RNA.
• indirectly through local growth factors and cytokines.TNF-α and IL-1 play the most important role in the initial step of bone resorption in estrogen deficient women.

 Estrogen plays its role in all the phases of bone loss in postmenopausal women…In EARLY ACCELERATED PHASE –most apparent during first decade after menopause and involves disproportionate loss of cancellous bone-is due to loss of direct restraining effect of estrogen on bone cell function.The next phase-LATE SLOW PHASE-continues throughout the life and involves proportionate loss of cancellous and cortical bone-is due to loss of effect of  estrogen on the extraskeletal  calcium homeostasis  which results in calcium wasting and an increased requirement for  dietry calcium intake to maintain bone loss.

Consequences of Decreased Bone Mass

The decreased bone mass leads to FRAGILITY  FRACTURES especially  of vertebral column,hip,ribs or wrist.These fractures may be asymptomatic or are related to acute or chronic pain pertaining to their extent, severity and on the current bone status.Menopause is among the non modifiable risk factors for osteoporotic bone fractures.

APPROACH TOWARDS MANAGEMENT

DIAGNOSIS

The first step towards managing a case of postmenopausal osteoporosis is diagnosing her as this.In this regard first of all identify in her the extent of risk of becoming osteoporotic , exclude the secondary causes of low bone mineral density (primary hyperthyroidism, dietry vitamin D defeciency, less exposure to sunlight, malabsorption and multiple myeloma etc) particularly if z score (the number of standard deviations from mean for a specific age and sex specific referrence group) is less than 2.00, and employing a number of conventional methods as given below

  Dual energy X-ray absorptiometry

Dual energy X-ray absorptiometry (DXA, formerly DEXA) is considered the gold standard for the diagnosis of osteoporosis. Osteoporosis is diagnosed when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a T-score. The World Health Organization has established the following diagnostic guidelines

• T-score -1.0 or greater is "normal"
• T-score between -1.0 and -2.5 is "low bone mass" (or "osteopenia")
• T-score -2.5 or above is osteoporosis

Biomarkers

Markers for bone turnover are incresed in serum and urine as bone remodeling is accelerated  in postmenopausal women.They include

• Serum alkaline phosphatase and osteocalcin;
• excretory products of type-1 collagen  such as hydroxyproline or pyridinoline cross-links of collagen.

Quantitative Computed Tomography

It gives separate estimates of BMD for trabecular and cortical bone and reports precise volumetric mineral density in mg/cm3 rather than BMD's relative Z score.
Among QCT's advantages:

• It can be performed at axial and peripheral sites.
• It  can be calculated from existing CT scans without a separate radiation dose.
• Is sensitive to change over time.
• It  can analyze a region of any size or shape, excludes irrelevant tissue such as fat, muscle, and air.
• It  does not require knowledge of the patient's subpopulation in order to create a clinical score (e.g. the Z-score of all females of a certain age).

Among QCT's disadvantages:

• It requires a high radiation dose compared to DXA.
• As  its practice has been less standardized than BMD so its results are more operator-dependent.
• Peripheral QCT has been introduced to improve upon the limitations of DXA and QCT.

   Quantitative ultrasound

The calcaneus is the most common skeletal site for quantitative ultrasound assessment because it has a high percentage of trabecular bone that is replaced more often than cortical bone, providing early evidence of metabolic change. The method can be applied to children, neonates, and preterm infants, just as well as to adults.

Conventional radiography

Osteoporotic bones will be visible as radiolucent and will show cortical thining.

TREATMENT

Non-pharmacological approach

• Calcium supplementation should be adjunctive treatment for all women with established osteoporosis and must be part of any preventive strategy to ameliorate bone loss. Increased calcium intake reduces the hyperparathyroidism associated with advancing age and can enhance mineralization of newly formed bone.A total calcium intake of 1200 to 1500 mg per day (through diet, supplements, or both) is recommended for all postmenopausal women.
• Vitamin D is essential for skeletal maintenance and enhancement of calcium absorption.Daily requirements for post-menopausal  women are 600-800IU (15-20µg) taken daily at any time of the day.  
• Regular physical activity, including aerobic, weight-bearing, and resistance exercise, is effective in increasing bone mineral density of the spine and strengthening muscle mass in postmenopausal women.

Pharmacological approach

1. Antiresorptive agents

• Post-menopausal hormone replacement therapy:  oral conjugated equine estrogen (reduces risk of vertebral, non-vertebral and hip fractures) and oral or transdermal  17-β estradiol.
• Selective estrogen receptor modulator:  Rloxifene (reduces risk of vertebral fractures only as it increases the spine bone mineral density).
• Bisphosphonates: The bisphosphonates are the most widely prescribed antiresorptive agents and are often considered first-line therapy for the treatment of postmenopausal osteoporosis. These agents suppress resorption by inhibiting the attachment of osteoclasts to bone matrix and enhancing programmed cell death. These are given orally and include alendronate and risedronate for  vertebral, non vertebral and hip fractures whereas ibandronate  for vertebral fractures specifically.
• Calcitonin: is an endogenous peptide that partially inhibits osteoclast activity. Nasal calcitonin and subcutaneous calcitonin are approved for the treatment of postmenopausal osteoporosis.

2. Anabolic agents

Subcutaneous PTH (1-34) (teriperatide) given daily for vertebral and non vertebral fractures.

PREVENTION

• Cessation of smoking and alcohol intake.
• Proper calcium and vitamin D intake.
• Regular exercise.

Posted in: Articles,diseaes,health,postmenopausal osteoporosis,treatments