Aging parathyroid hormone

Typical changes in bone mineral density with time after the onset of menopause, with and without treatment. In the untreated condition, bone is lost during aging in both men and women. Fluoride, strontium (Sr2+), and parathyroid hormone (PTH) promote new bone formation and can increase bone mineral density in subjects who respond to it throughout the period of treatment, although PTH also activates bone resorption. In contrast, estrogen, calcitonin, and bisphosphonates block bone resorption. This leads to a transient increase in bone mineral density because bone formation is not initially decreased. However, with time, both bone formation and bone resorption are decreased with these pure antiresorptive agents, and bone mineral density reaches a new plateau. 

Other target organs for the action of 1,25-dihydroxyvitamin D include the kidneys, bone, muscle,vwand skin. The hormone promotes reabsorption of both Ca2+ and inorganic phosphate by kidney tubules. In bone it binds to a specific receptor where it promotes the mobilization of calcium ions. This effect may result in part from stimulation of calcium-activated ATPase of the outer membrane of bone cells. Dissolution of bone also requires the presence of parathyroid hormone (PTH), the 83-residue hormone secreted by the parathyroid gland. In women past the age of menopause and in elderly men the production of 1,25-dihydroxyvitamin D decreases.w This may be a cause of the serious bone loss (osteoporosis) frequently observed. Treatment with 1,25-dihydroxyvitamin D3 or a synthetic analog seems to be helpful to such individuals. /Xy See also Chapter 30, Section A,5. 

Osteoporosis Generalized bone demineralization often associated with effects of aging and hormonal changes in postmenopausal women Calcium supplements, vitamin D, calcitonin, bisphosphonates, intermittent parathyroid hormone, estrogen, or SERMs (raloxifene] (see Chapter 30]... 

Kalu DN, Hardin RH, Cockerham R, Yu BP. Aging and dietary modulation of rat skeleton and parathyroid hormone. Endocrinology 1984 115 1239-1247. 

Teriparatide (a recombinant human parathyroid hormone) stimulates bone formation and is given daily by subcutaneous injection. There is evidence that teriparatide reduces vertebral and non-vertebral fractures. NICE recommends that it should be considered for the secondary prevention of osteoporotic fragility fractures in women aged 65 years and over who are intolerant of... 

Immunoreactive parathyroid hormone concentrations may be increased by anticonvulsants, while bone mineral content is reduced. Hypocalcemia and osteopenia can occur, despite normal serum concentrations of active vitamin D metabolites, suggesting that they may be independent of drug effects on vitamin D metabolism. Bone biopsies have shown increased osteoid but normal calcification front formation, accelerated rate of mineralization, and reduced mineralization lag time, suggesting increased skeletal turnover rather than osteomalacia (96). The risk of age-related fractures in drug-treated epileptic patients is not greatly increased (97). 

Endres DB, Morgan CH, Garry PJ, Omdahl JL. Age-related changes in serum immunoreactive parathyroid hormone and its biological action in healthy men and women. J Clin Endocrinol Metab 1987 65 724-31. 

Gallagher JC, Riggs BL, Jerpbak CM, Arnaud CD. The effect of age on serum immunoreactive parathyroid hormone in normal and osteoporotic women. J Lab Clin Med 1980 95 373-85. 

Stewart AF, Broadus AE. Clinical review 16 parathyroid hormone-related proteins coming of age in the 1990s. J Endocrinol Metab 1990 71 1410-4. 

Kalu, D. N., and R. H. Hardin. 1984. Age, strain and species differences in circulating parathyroid hormone. Hormone and Metabolic Research 16 654—657. 

Examples of cell populations are osteoblasts, which undergo apoptosis and are depleted with increasing age. A directed change in that program will prevent osteoporosis by reducing bone loss and increasing bone mass. The classical approach, i.e. application of parathyroid hormone (PTH), will be superseded by gene therapy. 

The intake of calcium, which if consumed in an amount of 1500 mg/d by postmenopausal women has been reported to be an effective preventative of aging bone loss (Heaney, 1981), has little effect on cortical thinning in adult mice unless consumed in a very limited amount (0.1% of the diet). This adaptability is attributable to the vitamin D-de-pendent, parathyroid hormone-mediated increase in calcium absorption which occurs at low calcium intakes. 

A 74-year-old woman, who was referred for evaluation of pain and persistently abnormal exposure of jaw bone after extraction of teeth, had been using weekly oral alendronate for osteoporosis for about 5 years. She had the clinical features of bisphosphonate-associated osteonecrosis of the mandible, which was precipitated by extraction of teeth 14 months before she was referred for assessment. She had multiple susceptibility factors for osteonecrosis of the jaw, including older age, type 2 diabetes mellitus, and a long duration of bisphosphonate therapy. The mandibular lesions did not improve despite repeated operations over 14 months. Bisphosphonate therapy was withdrawn and parathyroid hormone therapy was started after 2 months the oral mucosa had healed, after 4 months the pain had completely subsided, and after 6 months the patient s eating and drinking habits had returned. The serum concentration of osteocalcin, a marker of bone formation, which was initially suppressed, increased by 174% from baseline after 6 months of treatment with parathyroid hormone. 

The osteoporotic studies are now being extended to analysis of effects of a variety of widely used therapies compared with the properties existing in age-matched controls that did not have osteoporosis. Analyses of multiple sites in biopsies from larger numbers of women and men with osteoporosis showed a decrease in mineral matrix ratio, an increase in crystallinity, and an increase in collagen maturity.12-15 Hormone replacement therapy15 and parathyroid hormone16 shift the osteoporotic bone closer... 

A hormone is a messenger that causes tissue, organ, and cellular activities to increase or decrease tissue equal to the amount of the hormones in the blood. Disease and aging cause inappropriate secretion of hormones, resulting in abnormal tissue, organ, and cellular activities. Hormonal therapy is used for hormones produced by the pituitary, thyroid, parathyroid, and adrenal glands and restores hormonal balance by either ... 

Hyperparathyroidism results from oversecretion of PTH. This condition leads to excessive bone turnover and demineralization and must be treated by removal of the parathyroid gland. The disorder is classified into primary, secondary, and tertiary hyperparathyroidism. Sporadic primary hyperparathyroidism is the third most common endocrine disorder, after diabetes and hyperthyroidism. It is most common in females older than 55 years of age and the leading cause is a single adenoma, which secretes the hormone constitu-tively, without regulation. Symptoms can include osteopenia and bone fractures, renal stones resulting from hypercalciuria, peptic ulcer disease, and pancreatitis. In milder cases, patients are asymptomatic or suffer only muscle weakness, fatigue, and/or depression. 

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