Hyperadrenalism, or chronic glucocorticoid excess, whether endogenous (Cushing syndrome) or iatrogenic, leads to decreased bone mass. Glucocorticoid therapy results in a transient increase in bone resorption followed by a suppression of bone formation. Glucocorticoids decrease intestinal absorption of calcium. This stimulates the PTH–vitamin D endocrine axis to restore the serum concentration of ionized calcium by increasing bone resorption.

The combined direct and indirect effects of glucocorticoids often result in osteoporosis that is more severe in the axial than in the appendicular skeleton. Numerous guidelines have been published for the prevention and treatment of glucocorticoid-induced osteoporosis. Drugs approved for the prevention and treatment of glucocorticoid-induced osteoporosis include alendronate, risedronate, zoledronate, and teriparatide.

Nutritional. Various nutritional deficiencies can lead to osteoporosis. Adequate nutrition is critical during the accrual of peak bone mass when in a short period of time 40% of bone mass is acquired. Calcium is the principal mineral in bone. Chronic dietary deficiencies in calcium increase bone loss through PTH-mediated increase in bone remodeling. Dairy products are the major source of calcium. Total calcium intake in diet or supplements should be between 1000 and 1500 mg/day. Other food groups may affect bone health by altering acid-base balance; fruits and vegetables favor an alkaline environment, whereas meats favor an acid environment, which is buffered in bone and increases calcium loss in the urine. Dietary salt increases urine calcium excretion because sodium and calcium share transport pathways in the kidney. Adequate vitamin D is important because vitamin D deficiency decreases calcium absorption and increases PTH levels, which increases bone resorption. The major source of vitamin D is conversion of 7-dehydrocholesterol by sunlight in the skin. Very few foods contain vitamin D; fish and fish liver oils are the richest source. Vitamin D supplementation with between 400 and 1000 IU/day is recommended.

Alcoholism increases the risk for fractures. The development of osteoporosis is related to increase fall risk, poor nutrition, renal loss of calcium, and hypogonadism. In addition, ethanol decreases osteocalcin levels, a marker of osteoblast function.

Anorexia nervosa is prevalent in adolescents, affecting 0.2% to 1.0% of girls. Between 50% and 75% of patients with anorexia will have low bone mass for age. The mechanisms include amenorrhea and hypogonadism, increased levels of cortisol, and metabolic acidosis. The most effective treatment is correction of the eating disorder and resumption of menses.

Drug-Induced Bone Loss. Long-term glucocorticoid therapy is the most common cause of drug-induced osteoporosis. Use of the anticoagulant heparin may lead to osteopenia. Androgen deprivation and estrogen deprivation therapies (GnRH analogs and aromatase inhibitors) reduced bone mass by inducing hypogonadism. Anticonvulsants such as phenytoin and phenobarbital reduce vitamin D levels by increasing vitamin D metabolism. Serotonin reuptake inhibitors have been reported to increase fractures (serotonin has a role in bone metabolism) as have proton pump inhibitors, which may inhibit calcium absorption.

Disuse Osteoporosis. Weight-bearing exercise stimulates bone formation. Osteocytes have a mechanotransduction role and translate mechanical loading to cellular signals that stimulate osteoblast activity. After immobilization, bone density decreases rapidly. Nogravity environments such as spaceflight result in a loss of 1% to 2% of bone mass every month, a rate 10 times normal. Disuse osteopenia is common in degenerative lower motor neuron disease and in paraplegia and quadriplegia resulting from spinal cord injury.