Studies on osteoporosis X. Effect of estrogen-progestin combination on heparin-induced osteoporosis

Neutron activation analysis was employed to determine total body calcium in C₃H/St(Ha) female mice. As 99% of body calcium is in bone, loss of calcium was used as an index of bone loss (osteoporosis). Heparin (500 U/kg b.i.d. caused bone loss in 3 months. Premarin (2 mg/kg q.d.) or norethindrone (40 mg/kg q.d.) alone prevented this osteoporosis. A Premarin-norethindrone combination (2 mg – 10 mg q.d. respectively) appeared to be somewhat more effective than either agent alone, but this difference was not significant at the 5% level. Combinations of estrogen and progestins may prevent metabolic bone disease at the same time reducing the danger of estrogen induced neoplasia.     

Studies on osteoporosis VII. effect of 17β-hydroxy-4-estren-3-one 17-decanoate on experimental osteoporosis: A preliminary report

Total body neutron activation analysis was employed to measure total calcium in C₃H/St(Ha) female mice. Ninety-nine percent of total body calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg B.I.D.) treatment for three months resulted in significant osteoporosis. 17β-Hydroxy-4-estren-3-one 17-de-canoate 1.5 mg/kg or 4 mg/kg twice monthly prevented this heparin accelerated osteoporosis. The results suggest that 17β-hydroxy-4-estren-3-one 17-decanoate may be capable of preventing bone loss and partially increasing bone mass in patients exposed to osteoporosis inducing regimens.     

Understanding osteoporosis.

Considerable progress has been achieved recently in our understanding of the normal process by which bone mass is regulated. Age-related trabecular bone loss is characterized not simply by a global loss of bone but also by cortical porosity and loss of trabecular connections. Because bone strength depends on architectural as well as material properties, bone quantity alone cannot define fracture risk with precision. Traditional therapies for osteoporosis increase bone mass, and estrogen therapy, in particular, profoundly decreases fracture risk. The pharmacologic restoration of bone quantity and quality, however, remains elusive. Modern biotechnology offers the hope that progress may come about through the development of growth factors and other osteotropic compounds for clinical use.     

Overview of osteoporosis.

Osteoporosis is a common age-related disorder manifested clinically by skeletal fractures, especially fractures of the vertebrae, hip, and distal forearm. The major cause of these fractures is low bone mass, although an increase in trauma due to falls in the elderly also contributes. There are multiple causes for the low bone mass which, in any given individual, may contribute differently to the development of the osteopenia. The most important groups of causes are failure to achieve adequate peak bone mass, slow bone loss due to processes relating to aging, the menopause in women, and a variety of sporadic behavioral, nutritional, and environmental factors that affect bone mass in some but not in other individuals. The most important approach is prevention. Drugs and behavioral factors known to cause bone loss should be eliminated and perimenopausal women should be evaluated for possible preventive administration of estrogen. For patients with fractures due to established osteoporosis, the only drugs approved by the Food and Drug Administration are the antiresorptive agents calcium, estrogen, and calcitonin. Formation-stimulating regimens, however, are being developed and may be available for clinical use in the foreseeable future. These regimens may be capable of increasing bone mass to above the fracture threshold, thereby resulting in a clinical cure of the osteoporosis.     

Hibernation and disuse osteoporosis.

In an attempt to determine 1) if disuse osteoporosis occurs naturally during hibernation and 2) if it can be induced by limb immobilization in active and hibernating ground squirrels, forty-six thirteenlined ground squirrels were divided into five experimental groups. Group one was the active control group (AC) (ten animals). Group two was the active immobilized (AI) group and was subjected to a unilateral sciatic nerve section (ten animals). Group three was the hibernating control group and was allowed to hibernate undisturbed for 30 days (HC) (ten animals). The fourth group was subjected to a unilateral sciatic nerve section and allowed to hibernate for 30 days; this was the hibernating immobilized group (HI). The fifth group of six animals received the identical treatment as the (HI) group but was allowed to hibernate for 150 days.The following measurements were taken: Gastrocnemius-soleus mass, body mass, tibia-fibula weight, total tibia-fibula calcium and phosphorus. In addition, the femur was observed histologically for the enlarged lacunae typical of osteoporotic bone. Statistical analysis was accomplished with the Wilcoxan sign rank test.The data were interpreted to mean: 1) Disuse osteoporosis can be induced in active ground squirrels, 2) disue osteoporosis is not evident nor can it be induced by limb immobilization during 30 days of hibernation and 3) limb immobilization did not result in significant disuse osteoporosis following 150 days of hibernation. Only a few enlarged lacunae were evident after 150 days of hibernation.